Neuroendocrine neoplasia. Current concepts.
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Humans↗
Biomedical subjects
M R Wick
Publications and source records attributed to M R Wick.
Ruptured pulmonary infarction: a rare, fatal complication of thromboembolic disease.
We describe 2 men, ages 69 and 49 years, who experienced fatal rupture of pulmonary infarcts. Both patients had documented prior thromboembolic events and subsequently had abrupt deterioration in cardiorespiratory function. Autopsies showed massive unilateral hemothorax in both patients. Rupture of a pulmonary infarct may occur spontaneously or iatrogenically due to aggressive anticoagulation. This may be difficult to distinguish from secondary hemothorax with an intact pleura, but rupture typically has a considerably more rapid clinical evolution. Treatment should include immediate withdrawal of thrombolytic or anticoagulant medications and evacuation of the pleural space. Surgical intervention can be considered, although the utility of that approach must await prospective trials.
Aged↗
Neuroendocrine neoplasia of the lung.
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Humans↗
The role of immunohistochemistry in the diagnosis of malignant mesothelioma.
The immunohistochemical diagnosis of mesothelioma is perhaps one of the most perplexing and controversial issues in surgical pathology. A tumor that in essence is extremely rare has managed to captivate the attention not only of pulmonologists and thoracic surgeons but also of pathologists. Throughout its history, mesothelioma has emerged as one of the tumors that has evaded definitive characterization; hence, the numerous attempts at trying to establish not only histological criteria but also histochemical, immunohistochemical, and ultrastructural guidelines for its diagnosis. Perhaps as we enter an era of more sophisticated technology, molecular biology will have an opportunity to make inroads into the diagnosis and characterization of this peculiar neoplasm. Despite the many difficulties involved in the diagnosis of malignant mesothelioma, we have recently gained significant knowledge of this entity in many respects, several decades after its description. From a morphological point of view, several variations of the histological appearances that these tumors may exhibit have been described. Traditional histochemistry and electron microscopy continue to play an important role in the evaluation of these neoplasms, with ultrastructural analysis in particular representing the most reliable technique for making this diagnosis in equivocal cases. However, because of its speed, cost-effectiveness, and general availability, immunohistochemistry has emerged as the most commonly used procedure for the diagnosis of mesotheliomas. We herein present a review of the current status of immunohistochemical evaluation of malignant lesions that are suspected of having a mesothelial lineage.
Adenocarcinoma↗
Immunohistologic evaluation of metastatic carcinomas of unknown origin: an algorithmic approach.
Pathologists are now asked frequently to determine the primary site for metastatic carcinomas of unknown origin (MCUO), using adjunctive morphological techniques such as electron microscopy, immunohistology, and other modalities. The authors present an algorithmic immunohistochemical approach to this problem that is based on their experience with over 2,800 routinely-processed epithelial malignancies of various types. These have been studied with antibodies to keratins, vimentin, epithelial membrane antigen, MOC-31, tumor associated-glycoprotein-72 (recognized by monoclonal antibody B72.3), prostate-specific antigen, thyroglobulin, gross cystic disease fluid protein-15, carcinoembryonic antigen, CA-125, CA19-9, placental alkaline phosphatase, S100 protein, and estrogen receptor protein. The algorithm that is structured around these 14 analytes is based on the relative predictive value of each marker, which in turn, determines its place in the sequence of interpretation. The authors' experience with this approach shows 67% accuracy with regard to the ultimately determined site of origin for MCUO, a figure which is similar to that reported by other investigators.
Algorithms↗
Immunohistology of neuroendocrine and neuroectodermal tumors.
Neuroendocrine and neuroectodermal tumors are interrelated, and comprise a neoplastic family including lesions formerly termed "carcinoid," "atypical carcinoid," "small cell undifferentiated carcinoma," "primitive neuroepithelioma," "chemodectoma," and "neuroblastoma," to name but a few entities. The nosology of these neoplasms has been simplified recently, in part as a result of a better understanding of their immunophenotypes and molecular biological attributes. This review considers those immunohistochemical markers that are now generally available for diagnostic evaluation of neuroendocrine and neuroectodermal differentiation, and provides information on the relative sensitivity and specificity of each of them. Intermediate filament proteins, chromogranins, synaptophysin, CD56, CD57, CD99, neuron-specific (gamma-dimer) enolase, protein gene product 9.5, and specific neuropeptide products are discussed. The application of such determinants in regional differential diagnosis is also summarized.
Algorithms↗
Lymphoepithelioma-like carcinoma of the skin with apparent origin in the epidermis--a pattern or an entity? A case report.
BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) is prototypically represented by "undifferentiated" nasopharyngeal carcinoma, but it has also been described in many other anatomic locations, including the skin. In the last of these sites, primary LELC has been assumed in the past to show dermal adnexal differentiation. METHODS: The authors present a case wherein LELC of the skin (LELCS) instead appeared to be a morphologic manifestation of squamous carcinoma of the skin surface, as supported by the results of immunohistology and in situ hybridization. RESULTS: Like other examples of LELCS, it showed no evidence of integration of the Epstein-Barr viral genome, and its behavior was indolent. CONCLUSIONS: The heterogeneous nature of LELC as seen in different body sites is reviewed in this report, resulting in the conclusion that this tumor probably represents a morphologic pattern rather than a distinct clinicopathologic entity.
Aged↗
Fine-needle aspiration cytology and immunohistology of low-grade adenosquamous carcinoma of the breast.
Low-grade adenosquamous carcinoma of the breast (LASCB) is a relatively recently-described, rare histotype of breast cancer that has a favorable prognosis. Its principal microscopic features are the presence of "syringoid" ("tadpole"-shaped) ductal profiles of tumor cells, a bland and modestly cellular stromal background, and the variable presence of keratinizing ("epidermoid") cell groups. As such, the basic image of LASCB is quite similar to that of microcystic adnexal or adenosquamous carcinoma of the skin or "syringomatous adenoma" of the nipple. We report the fine-needle aspiration cytologic (FNA) attributes of this neoplasm, as well as its immunohistochemical characteristics and differential diagnosis.
Biomarkers, Tumor↗
Thymic neuroendocrine tumors: a commentary with current perspectives on neuroendocrine neoplasia.
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Humans↗
The pathological distinction between "deep penetrating" dermatofibroma and dermatofibrosarcoma protuberans.
In selected cases, the clinicopathological distinction between deep penetrating dermatofibroma (DPDF), which involves the subcutis, and dermatofibrosarcoma protuberans (DFSPs) may be challenging. In most instances, attention to the cytological constituency of the lesions and the overall architecture is sufficient to make this separation. DPDF is typified by cellular heterogeneity, including giant cells and lipidized histiocytes; when it extends into the hypodermis, it does so either using the interlobular subcuticular fibrous septa as scaffolds or in the form of broad pushing fronts of tumor. In contrast, DFSP is a cytologically monotypical tumor, which entraps subcutaneous adipocytes diffusely or grows in stratified horizontal plates in the hypodermis. In the minority of cases where conventional morphological analysis of optimal biopsy specimens is diagnostically indeterminate, immunostaining for CD34 and factor XIIIa (FXIIIa) is helpful; it is also often necessary when a poorly-representative sample of the lesion has been obtained by the clinician. Characteristically, DF is diffusely FXIIIa-reactive and CD34-negative, whereas DFSP manifests the converse of those findings. Other markers such as Ki-M1p, mutant p53 protein, and metallothionein may also provide adjuvant diagnostic information in this context, as may the observation of abnormalities in chromosomes 17 and 22 by direct karyotypic analysis.
Dermatofibrosarcoma↗
Low-stage carcinoma of the male breast. A histologic, immunohistochemical, and flow cytometric comparison with localized female breast carcinoma.
Male breast carcinoma (MBC) accounts for only 1% of total mammary carcinomas. Controversy exists about whether MBC differs clinically and pathologically from female breast carcinoma (FBC). We compared 10 archival cases with 75 stage-matched FBCs. Clinical data, histologic details, immunostains for mammary lineage markers, and results of several putative "prognostic" analyses were addressed, including DNA ploidy and expression of c-erbB-2 (neu) oncoprotein and p53 protein. Cumulative literature data on 2,530 MBCs were contrasted with information from 135 institutional cases of FBC. A statistically significant difference in grade 3 lesions at low stage persisted when MBCs of all stages were compared with similar FBCs. For stages I and IIA, 5-year survival was 60% and 86% for MBCs and FBCs, respectively (also statistically significant). This difference disappeared when all stages were compared. A similar number of MBCs and FBCs, regardless of stage, demonstrated DNA aneuploidy with or without synthesis of S-100 protein, gross cystic disease fluid protein-15, c-erbB-2 protein, and p53 protein. Hormone receptor positivity was more common in MBC than in FBC at high tumor stages. Low-stage MBC and FBC differ biologically; MBCs tend to manifest at a higher grade with lessened 5-year survival. However, aside from distinctions in hormone receptor proteins, broader comparison of MBC and FBC at stages IIB and higher shows no significant differences in 5-year survival or expression of breast cancer-associated gene products.
Aged↗
Postoperative/posttraumatic spindle cell nodule of the skin: the dermal analogue of nodular fasciitis.
Spindle cell proliferations of the skin are diverse, both morphologically and mechanistically. The authors have encountered four examples of a distinctive reactive/reparative cutaneous spindle cell lesion that shows homology with ones seen in the genitourinary tract and oral cavity and that is known as "postoperative/posttraumatic spindle cell nodule" (PSCN). These occurred in the skin of the face and scalp (2 cases), arm (1 case), and vulvar skin (one case), and were clearly related historically to prior episodes of trauma. The proliferations were characterized by variably-apposed and cytologically-bland spindle cells with numerous mitotic figures, set in a highly vascular stroma containing extravasated erythrocytes and inflammatory cells. All lesions were immunoreactive for vimentin, actin, and desmin, with no labeling for keratin. Postoperative/posttraumatic spindle cell nodule of the skin is a significant pseudoneoplastic lesion that is related (and perhaps identical pathogenetically) to nodular fasciitis; as such, it may be mistaken for a sarcoma or a spindle cell carcinoma. Careful attention to clinicopathologic and histologic details should result in its accurate recognition.
Adult↗
Ectopic breast tissue and breast-like sweat gland metaplasias: an overlapping spectrum of lesions.
There are many similarities in the morphology of benign and malignant lesions of the sweat glands and the breasts. The recently described cutaneous mammary-like sweat glands, also known as mixed sweat glands or apoeccrine glands, are also a likely source of selected proliferations that closely mimic those of the breast. We present three cases of breast-like lesions arising in the skin that demonstrate the ways in which the morphologic and pathologic continuum of the mammary glands, cutaneous mammary-like glands, and sweat glands can produce difficulties in precise diagnosis. The examples demonstrate that an anatomic location outside the milk line does not preclude the diagnosis of ectopic mammary tissue, and that lesions closely resembling those of the breast may also arise outside the milk line from conventional sweat glands or mixed sweat glands. The concept of homologous lesions of the breast, breast-like glands and sweat glands, in which morphology is partially mirrored by biochemical similarities, provides a perspective for classification of problematic cases of breast-like cutaneous lesions.
Adult↗
Primary carcinomas of the thymus gland.
Carcinomas of the thymus are now well recognized as distinctive but rare entities, and several clinicopathologic variants of such neoplasms have been described. These include keratinizing squamous cell carcinoma, nonkeratinizing squamous cell carcinoma, lymphoepithelioma-like carcinoma, neuroendocrine carcinoma, adenosquamous carcinoma, mucoepidermoid carcinoma, clear-cell carcinoma, papillary adenocarcinoma, adenocarcinoma not otherwise specified, basaloid carcinoma, and sarcomatoid carcinoma. The application of electron microscopy, immunohistology, and other adjunctive pathological techniques is effective in refining the differential diagnosis between primary thymic carcinoma (PTC) and several other histological simulators. However, the distinction between PTC and carcinomas that involve the thymic region by metastasis from other sites is a difficult one, and ultimately must be predicated on detailed clinical and radiographic information. Well-differentiated squamous carcinoma, low-grade mucoepidermoid carcinoma, and basaloid carcinoma of the thymus usually are associated with a favorable prognosis, but other variants are aggressive and require multimodality treatment approaches.
Aged↗
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.
Adenoma, Oxyphilic↗
The impact of diagnostic immunohistochemistry on patient outcomes.
Diagnostic immunohistology (DIHC) is a discipline that has been used clinically for at least two decades, but, because of medicolegal encumbrances, it has not been a part of many formal outcomes analyses during that time. Potential applications of this technology with a direct bearing on response to treatment include the accurate identification of infectious organisms, distinction between morphologically-similar undifferentiated tumors, separation of benign and malignant neoplasms, and prognostication of malignancies. The first two of those four roles may indeed have a quantifiable impact on case outcomes, but the last two applications have only questionable value in this specific context. This is an area of medicine in which formal outcomes analysis is greatly needed to help determine future practice patterns.
Cost-Benefit Analysis↗
Invasion of the bladder by transitional cell carcinoma: its relation to histologic grade and expression of p53, MIB-1, c-erb B-2, epidermal growth factor receptor, and bcl-2.
BACKGROUND: Although pathologic level of invasion and histologic grade are helpful in predicting the clinical outcome of transitional cell carcinoma of the bladder, they also create uncertainty. Immunohistochemical staining for p53, MIB-1, epidermal growth factor receptor (EGFR), c-erb B-2, and bcl-2 have shown promise as prognostic factors when evaluated singly, although multivariate analyses that include histologic grade and the interactive effects of these markers have not been studied extensively. The authors have initiated a prospective study to determine whether these markers add prognostic information to that provided by level of invasion and histologic grade. This initial report details how these five markers relate to invasion of the bladder after controlling for the effects of histologic grade. METHODS: The authors evaluated 229 transitional cell carcinomas in 229 patients using the World Health Organization grading schema and immunohistochemical staining with antigen retrieval for p53, MIB-1, EGFR, c-erb B-2, and bcl-2, and they related these markers to invasion after controlling for grade with a multivariate logistic regression model. RESULTS: Although Grades 2 and 3 were the most important for predicting invasion, Grade 2 tumors that stained for either MIB-1 or p53 indicated a significantly greater probability of invasion than suggested by grade alone. bcl-2 and p53 had an opposing and interactive effect: when p53 was absent, the presence of bcl-2 implied less probability of invasion; but when both bcl-2 and p53 were present, the protective effect of bcl-2 was no longer observed. Although neither EGFR nor c-erb B-2 were as important as the other three markers in determining the risk of invasion, Grade 3 tumors that stained for one, and especially both, of these markers were less likely to be invasive. CONCLUSIONS: These five markers sort into three interactive pairs: MIB-1 and p53, bcl-2 and p53, and EGFR and c-erb B-2. MIB-1 and p53 together imply a greater probability of invasion. bcl-2 appears to have a dual role, which depends on the presence of accumulated p53. Finally, EGFR and c-erb B-2 related closely to each other and in Grade 3 tumors imply a lesser probability of invasion. It is likely that combinations of markers, or correlations between markers and grades, will yield prognostic information that is more powerful than what histologic grade alone can provide.
Biomarkers, Tumor↗
Homologous carcinomas of the breasts, skin, and salivary glands. A histologic and immunohistochemical comparison of ductal mammary carcinoma, ductal sweat gland carcinoma, and salivary duct carcinoma.
Morphologic mimicry among human malignant neoplasms is a well-known phenomenon in surgical pathology; both undifferentiated and "committed" neoplasms may exhibit this trait. One particularly common group of histologic simulants includes ductal carcinomas of the breasts, the cutaneous appendages, and the salivary glands. One hundred three tumors in this structural cluster were analyzed microscopically and immunohistologically to codify points of potential pathologic similarity and difference. All the lesions were typified by irregularly permeative clusters and cords of atypical polygonal cells with variable luminal differentiation. A proportion of primary neoplasms in each site demonstrated in situ ductal components; in the absence of the latter elements, however, it was not possible to make topography-related morphologic distinctions among them. Immunostains for gross cystic disease fluid protein-15 (GCDFP-15), carcinoembryonic antigen, S100 protein, c-erbB-2 oncoprotein, estrogen receptor protein, and progesterone receptor protein also showed largely overlapping phenotypes in each of the three tumor categories, with selected exceptions. These differences were elucidated through paired chi 2 analysis and included a statistically significant infrequency of GCDFP-15 in eccrine sweat gland carcinomas, a paucity of carcinoembryonic antigen in breast cancers, and an absence of estrogen receptor protein in salivary duct carcinomas. Such findings may be useful in predefined differential diagnostic settings involving the distinction between primary and metastatic ductal cancers of the breasts, skin, and salivary glands. Nevertheless, because of the striking homologies between such tumors at structural and protein-synthetic levels of comparison, it is mandatory that all available clinicopathologic information be used in this context.
Adenocarcinoma↗