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Context: - Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose., Objective: - To provide updated, practical guidelines for the pathologic diagnosis of MM., Data Sources: - Pathologists involved in the International Mesothelioma Interest Group and others with an interest and expertise in the field contributed to this update. Reference material included up-to-date, peer-reviewed publications and textbooks., Conclusions: - There was discussion and consensus opinion regarding guidelines for (1) distinguishing benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) recognition of the key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiating epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid MM, (7) use of molecular markers in the diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels employed is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Depending on the morphology, immunohistochemical panels should contain both positive and negative markers for mesothelial differentiation and for lesions considered in the differential diagnosis. Immunohistochemical markers should have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic and membranous markers). Selected molecular markers are now being used to distinguish benign from malignant mesothelial proliferations. These guidelines are meant to be a practical diagnostic reference for the pathologist; however, some new pathologic predictors of prognosis and response to therapy are also included.

Context: Evidence-based medicine has been proposed as a new paradigm for the identification and evaluation of medical information. Best available evidence or data are identified and used as the basis for the diagnosis and treatment of individual patients. Evidence-based pathology has adapted basic evidence-based medicine concepts to the specific needs of pathology and laboratory medicine., Objectives: To briefly review the history and basic concepts of evidence-based medicine and evidence-based pathology, describe how to perform and interpret systematic reviews, and discuss how to integrate best evidence into guidelines., Data Sources: PubMed (National Library of Medicine, Washington, DC) and Web of Science (Thompson Reuters, New York, New York) were used., Conclusions: Evidence-based pathology provides methodology to evaluate the quality of information published in pathology journals and apply it to the diagnosis of tissue samples and other tests from individual patients. Information is gathered through the use of systematic reviews, using a method that is less biased and more comprehensive than ad hoc literature searches. Published data are classified into evidence levels to provide readers with a quick impression about the quality and probable clinical validity of available information. Best available evidence is combined with personal experience for the formulation of evidence-based, rather than opinion-based, guidelines that address specific practice needs.

Context: Contrary to the intuitive impressions of many pathologists, several areas exist in laboratory medicine where evidence-based medicine (EBM) principles are not applied. These include aspects of both anatomic and clinical pathology. Some non-EBM practices are perpetuated by clinical "consumers" of laboratory services because of inadequate education, habit, or overreliance on empirical factors. Other faulty procedures are driven by pathologists themselves., Objectives: To consider (1) several selected problem areas representing non-EBM practices in laboratory medicine; such examples include ideas and techniques that concern metastatic malignancies, "targeted" oncologic therapy, general laboratory testing and data utilization, evaluation of selected coagulation defects, administration of blood products, and analysis of hepatic iron-overload syndromes; and (2) EBM principles as methods for remediation of deficiencies in hospital pathology, and implements for the construction of "quality" practices in our specialty., Data Sources: Current English literature relating to evidence-based principles in pathology and laboratory medicine, as well as the authors' experience., Conclusions: Evidence-based medicine holds the promise of optimizing laboratory services to produce "quality" practices in pathology. It will also be a key to restraining the overall cost of health care.

Context: Pseudoneoplastic cutaneous lesions are diverse, not only morphologically but also with respect to their causes and cellular lineages. They include proliferations of epithelial, as well as mesenchymal, elements., Objective: This review aims to consider selected lesions in the aforementioned groups, contrasting them with histologically similar neoplasms of the skin in a differential diagnostic setting., Data Sources: Information used in assembling this discussion was drawn from the published literature on cutaneous pseudoneoplasms, using an Internet-based search engine. The authors' collective experience was also used in writing this review., Conclusions: Sufficient clinical and morphologic differences exist in virtually all instances to separate pseudoneoplastic cutaneous proliferations from the tumors that they imitate.

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

Context: Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose., Objective: To develop practical guidelines for the pathologic diagnosis of MM., Data Sources: A pathology panel was convened at the International Mesothelioma Interest Group biennial meeting (October 2006). Pathologists with an interest in the field also contributed after the meeting., Conclusions: There was consensus opinion regarding (1) distinguishing benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiating epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid mesothelioma, (7) use of molecular markers in the differential diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels used is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Immunohistochemical panels should contain both positive and negative markers. The International Mesothelioma Interest Group recommends that markers have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic membranous markers). These guidelines are meant to be a practical reference for the pathologist.

Context: Selected cutaneous neoplasms share features with benign counterparts or have subtle morphologic features that could be overlooked by the pathologist., Objective: To present clues to the diagnosis of potentially deceptive malignancies, including desmoplastic malignant melanoma, nevoid malignant melanoma, subcutaneous lymphoma, metastatic breast carcinoma, and epithelioid sarcoma., Data Sources: Published literature and personal experience., Conclusions: Knowledge of commonly misdiagnosed cutaneous neoplasms will help the general surgical pathologist avoid these potential pitfalls in neoplastic dermatopathology.

Objective: Currently, the bronchiolitis obliterans syndrome (BOS) of chronic airway rejection represents the most significant obstacle to the long-term function of isolated pulmonary allografts in humans. Between 20% and 30% of recipients are affected by this condition. To define the possible pathogenetic role of altered expression of class II major histocompatibility complex antigens (ie, HLA-DR) in BOS, the authors studied well-characterized examples of this process immunohistologically., Design: Eleven BOS specimens were compared with seven controls, represented by allografts with no pathologic abnormalities taken from patients with normal posttransplant respiratory function, as well as 14 biopsies showing acute rejection. In addition, immunophenotypic subtyping of lymphocytes in all specimens was undertaken., Results: Control tissues exhibited variable but weak expression of HLA-DR in bronchiolar epithelium and alveolar pneumocytes. In comparison, immunostaining for class II major histocompatibility complex antigens in BOS showed no statistically significant differences, whereas the 14 examples of acute rejection manifested intense HLA-DR expression in epithelia and endothelial cells. The numbers of intrabronchiolar and peribronchiolar lymphocytes were clearly higher in both acute rejection and BOS than in controls, but these cells differed in lineage in the two rejection states. Acute rejection showed an obvious preponderance of CD43-positive T lymphocytes, whereas lymphoid cells in BOS were a relatively equal mixture of CD20-positive B cells and CD43-positive T cells. Moreover, incipient peribronchiolar B-cell follicles were observed in BOS. Natural killer (CD57-positive) lymphocytes were rare in all specimens., Conclusions: These data suggest that alterations in HLA-DR expression probably do not play a central role in the genesis of BOS, as they do in acute rejection. In contrast, the results of lymphocyte immunophenotyping and correlative histologic findings in BOS suggest that both T cells and B lymphocytes may be involved in the mechanism of chronic airway rejection.

Identification of contaminating tissue fragments as "floaters" is a common problem in surgical pathology. They may be introduced at several steps in the processing of specimens, and they are capable of causing interpretative consternation. Using immunohistochemistry with monoclonal antibodies to blood group isoantigens A, B, and H, we studied nine cases in which floaters were present. In five of the study cases, discordant blood group immunostains allowed identification of the artifactual tissue fragments. By chance, the other four specimens contained probable floaters from patients whose blood groups were concordant with those from whom the "native" tissue had been obtained. These results indicate that in some instances, blood group immunostains may resolve interpretative difficulties surrounding floaters. It is likely that application of immunostains, directed at additional blood group antigens, will extend the utility of this procedure.

Chordoma is a distinctly uncommon neoplasm in the first two decades of life. To characterize further its clinicopathologic features in this age group, we studied 12 chordomas from six males and six females (age range, 1 month to 20 years at diagnosis), with a mean age of 6 years. Six tumors arose in the clivus, four in the cervical or thoracic vertebrae, and two in the lumbar and sacrococcygeal areas. The clinical presentations reflected the location. Histologically, six cases were classic chordomas; the remaining six had atypical or nonclassic features of a round cell or spindle cell tumor. Immunohistochemical stains for vimentin and cytokeratin were positive in all cases tested, whereas epithelial membrane antigen was detected in 11 examples, and S100 protein reactivity was noted in nine lesions. The tumors were uniformly nonreactive for glial fibrillary acidic protein and carcinoembryonic antigen. Electron microscopy in six cases demonstrated large primitive cells with attenuated cell junctions, whorls of cytoplasmic filaments, vacuoles, and glycogen aggregates. Ten children had died of tumor at intervals of 3 weeks to 4.5 years after diagnosis and treatment. Lung, lymph nodes, and other organs were the distant metastatic sites in seven cases. These findings imply that chordomas in children are more variable histologically and may pursue a more aggressive clinical course than their adult counterpart. Immunohistochemical studies are particularly helpful in the differentiation of atypical chordomas from other round and spindle cell neoplasms.

Epidemiologic features of well-differentiated thyroid tumors and experimental evidence suggest that female sex hormones may exert effects on this gland and its neoplasms. This possibility was addressed by investigating the expression of estrogen-receptor protein in 80 thyroid neoplasms. Patients with papillary carcinomas, follicular carcinomas, and follicular adenomas were selected from each of the following groups: (1) postpubertal-premenopausal women (who are associated with the most favorable prognosis and greatest incidence of these neoplasms); (2) postmenopausal women; and (3) men of various ages. Sections from formalin-fixed paraffin-embedded tumors were stained with antiestrophilin antibody (clone H222) and the avidin-biotin-peroxidase complex method. In addition, other markers were included to distinguish thyroidal from other estrogen-receptor protein-reactive neoplasms; an anticytokeratin mixture, antithyroglobulin, and anti-gross cystic disease fluid protein-15 were applied in all cases. The expression of estrogen-receptor protein was detected in eight of 10, six of 10, and nine of 10 papillary carcinomas; four of eight, two of seven, and one of five follicular carcinomas; and none of 10, none of 10, and two of 10 follicular adenomas, in groups 1, 2, and 3, respectively. Nuclear staining was regional or multifocal in distribution. Cytokeratin and thyroglobulin were detected in all tumors. In contrast, none displayed anti-gross cystic disease fluid protein-15 immunoreactivity. These results indicate that the estrogen receptor may be detected immunohistochemically in thyroid neoplasms. However, no differences that could account for possible estrogen-related epidemiologic and prognostic variation in such tumors could be ascertained. Other discriminating immunostains, primarily including anti-gross cystic disease fluid protein-15 and thyroglobulin, are effective in distinguishing between thyroidal and extrathyroidal tumors that may express estrogen-receptor protein.

Microglandular adenosis (MA) of the breast is a benign, disorganized proliferation of glands lined by a single layer of cells. As such, differential diagnosis between MA and tubular carcinoma may be challenging in selected cases. A panel of antibodies was applied to 10 cases of MA and 10 of tubular carcinoma to investigate the potential benefit of immunohistochemistry in the separation of these lesions and the possible role of myoepithelial cells in MA. The luminal cells in nine cases of MA were surrounded by a cuff of muscle-specific actin-reactive cells, which also coexpressed cytokeratin and vimentin. The immunophenotype of these cells is characteristic of myoepithelial differentiation, which was heretofore thought to be lacking in MA. This finding demonstrates that myoepithelial cells are indeed present in MA subjacent to luminal epithelial cells; moreover, it distinghuishes MA from tubular carcinoma, all examples of which were actin negative in this analysis. In addition, circumferential type IV collagen deposition was observed around constituent glands of MA in nine cases but was lacking in all tubular carcinomas. Other markers included in this evaluation (S100 protein, gross cystic disease fluid protein 15, carcinoembryonic antigen, estrogen receptor protein) were of no differential diagnostic value.

Tumefactive fibroinflammatory lesion is an idiopathic fibroinflammatory process of the head and neck region. Although benign histopathologically, it is invasive, destructive, and locally recurrent, leading to uncertainty regarding its proper management; as the disease is rare, determining optimal treatment is difficult, given the anecdotal nature of reports. We report the first case of a tumefactive fibroinflammatory lesion occurring outside the head and neck region. Our patient was treated with corticosteroids and had a favorable response, supporting this approach as initial treatment. Immunohistochemical studies performed on a pretreatment specimen were consistent with a secondary inflammatory component because no monoclonal nor aberrant phenotypes were detected. The tumefactive fibroinflammatory lesion appears to be indistinguishable from the other known idiopathic fibroinflammatory processes; patients presenting with any one of these should be evaluated for the others.

Gross cystic disease fluid protein-15 (GCDFP-15) is a 15-kd glycoprotein that is expressed by normal apocrine epithelia and in a majority of breast carcinomas. However, recent studies have demonstrated that this substance is also present in tumors of the salivary glands, sweat glands, and prostate gland. To determine whether the expression of CGDFP-15 might aid in the differential diagnosis of salivary gland lesions, the anti-GCDFP-15 monoclonal antibody D6 was applied to paraffin sections of 133 such neoplasms. Benign tumors (76% reactive) were more often labeled than malignant lesions (28% reactive) by this antibody; overall, 53 (41%) of 133 cases were positive for GCDFP-15. Notably, the tubuloglandular components in 17 (81%) of 21 pleomorphic adenomas were reactive, but no example of either adenoid cystic carcinoma or polymorphous low-grade adenocarcinoma were labeled. In contrast, 24% of adenocarcinomas stained with this antibody. The apparent expression of GCDFP-15 by a spectrum of salivary gland tumors supports their biologic relationship to lesions of the cutaneous apocrine glands and breast. Furthermore, the demonstration of this determinant may be of use in suggesting the salivary gland nature of poorly differentiated carcinomas of the head and neck, and it may facilitate the separation of pleomorphic adenoma from histologically similar malignant neoplasms in the salivary glands themselves.

Mesenchymal chondrosarcoma is an uncommon small-cell neoplasm of bone and soft tissue, the chondrogenic nature of which has been generally accepted. However, the phenotypic attributes of the small-cell population in this neoplasm have not been well characterized, and its relationship to "precartilage mesenchyme" remains unclear. In an attempt to address this issue, we performed an immunohistochemical analysis of nine cases, using antibodies to vimentin, S100 protein, Leu-7 antigen, neuron-specific enolase, synaptophysin, desmin, muscle-specific actin, cytokeratin, and epithelial membrane antigen, and the avidin-biotin-peroxidase complex (ABC) method. The small cells of mesenchymal chondrosarcoma failed to express S100 protein, whereas all components of the tumors (small cells, lacunar chondroblasts, and chondroid matrix) stained for Leu-7 antigen in six cases. Neuron-specific enolase was identified in the small cells of four cases and in the lacunar cells of seven. None contained desmin, actin, cytokeratin, epithelial membrane antigen, or synaptophysin. The immunophenotype of mesenchymal chondrosarcoma resembled that of embryonic cartilage and thus did not contradict the premise that this tumor was the neoplastic counterpart of fetal chondroid tissues. However, immunohistologic studies are not overly helpful in the differential diagnosis between mesenchymal chondrosarcoma and other small round cell lesions.

Sweat gland carcinomas constitute less than 10% of all malignant tumors of the vulva, including those associated with extramammary Paget's disease (EPD). The histopathologic diagnosis of vulvar sweat gland carcinomas is difficult because of their rarity; their resemblance to metastatic carcinomas of the internal female genitalia, kidneys, and other sites; and their diversity of microscopic appearances. We report five examples of vulvar sweat gland carcinomas, two of which were associated with EPD. The other tumors included one example each of ductal eccrine adenocarcinoma, eccrine porocarcinoma, and clear cell hidradenocarcinoma. The clinical behavior of these neoplasms is correlated with their histologic types; we also discuss differential diagnosis and treatment recommendations.

Fewer than 100 cases of primary leiomyosarcoma of the lung have been reported, few of which have been studied by electron microscopy. We performed clinicopathologic studies, including fine structural analysis, of two such cases. Their ultrastructural features differed in part from those of other smooth-muscle tumors, which may help exclude other malignant pulmonary lesions from the differential diagnosis.

A primary duodenal small-cell neuroendocrine carcinoma was found in an elderly man who presented with upper abdominal pain. Although metastatic small-cell carcinoma was documented by liver biopsy, the primary lesion was not identified until postmortem examination. The latter tumor, which ulcerated the duodenal mucosa, was composed of small ovoid cells with sparse cytoplasm and granular chromatin. Electron microscopy revealed cytoplasmic dense-core granules. Immunocytochemical study demonstrated the presence of neuron-specific enolase, Leu 7 antigen, chromogranin, epithelial membrane antigen, and vasoactive intestinal polypeptide within tumor cells. However, there was no evidence of a clinical endocrinopathy. This case emphasizes the need to include the duodenum as a possible primary site when metastatic small-cell neuroendocrine carcinoma is seen in the absence of apparent pulmonary disease.

This study compares the immunoprofiles of 25 cutaneous and mucosal melanomas with those of 400 poorly differentiated carcinomas, using a polyclonal antiserum to S100 and murine monoclonal antibodies to keratin (KER) and epithelial membrane antigen (EMA). All malignant melanomas expressed S100 but lacked reactivity for KER and EMA. Conversely, all of 49 carcinomas (12%) that displayed S100 also exhibited positivity for both epithelial markers. The latter group of tumors included 17 carcinomas of the breast, 16 eccrine sweat gland carcinomas, five high-grade salivary glandular adenocarcinomas, four lung cancers, three pancreatic ductal carcinomas, two serous ovarian carcinomas, one clear cell adenocarcinoma of the bladder, and one uterine cervical squamous carcinoma. None of 32 epithelial neoplasms that lacked both KER and EMA (19 testicular seminomas, four hepatocellular carcinomas, eight adrenocortical carcinomas, and one Merkel's cell carcinoma) contained S100 protein. These results suggest that S100 protein is relatively nonspecific as a single immunodeterminant in the diagnostic separation of melanoma and anaplastic carcinoma. The concomitant use of stains for EMA and KER, however, obviates this problem. Finally, since it is somewhat restricted in distribution, S100 reactivity in a known carcinoma may be of some use in predicting possible primary sources for a metastasis of unknown origin.

We treated two patients who had lesions in the prostate with histologic features similar to those of cystosarcoma phyllodes of the breast. In one case, the stroma progressed to a clearly sarcomatous appearance, whereas the other tumor had a cellular stroma that was mitotically inactive. This element was immunoreactive for vimentin and desmin in both cases but was negative for epithelial markers. In contrast, the epithelial component was immunoreactive for prostate-specific antigen and epithelial membrane antigen. Following surgical resection, both patients were well two and three years later, without local recurrence or distant metastasis. The histogenesis of these tumors is unknown.

We report two cases of adult patients with primary tumors in the nasopharynx and paranasal sinuses, which were characterized histologically by areas of transitional cell (cylindric or "schneiderian") carcinoma and other foci virtually indistinguishable from endodermal sinus tumor (yolk sac carcinoma). Immunohistochemical studies supported the impression of yolk sac differentiation. Both patients were treated with irradiation and multidrug chemotherapy. One patient died of uncontrollable recurrence of tumor, whereas the other developed locally recurrent, transitional cell carcinoma in the absence of yolk sac tumor. The concurrence of these patterns of carcinoma, which has been undescribed previously to the best of our knowledge, seems to be associated with more aggressive biologic behavior than pure transitional cell carcinomas of this region.

Transitional cell carcinomas of the urinary tract may occasionally assume a partial or complete spindle cell pattern of growth, leading to the erroneous classification of some true carcinomas as sarcomas. We have recently observed two such tumors of the renal pelvis. In these cases, ultrastructural study showed that the spindle cells retained features of epithelial differentiation; this conclusion was further supported by positive results of several immunohistochemical stains, using biotinylated peanut agglutinin and soybean agglutinin, and a rabbit antiserum directed against keratin proteins. In addition, both tumors manifested immunoreactivity for blood-group antigens, using primary murine monoclonal antibodies. The results of these studies suggest that immunocytochemistry is a helpful diagnostic adjunct in the proper classification of sarcomatoid urothelial neoplasms.

The histogenesis of a distinctive metastasizing intramural gastric tumor found in patients with extra-adrenal paragangliomas, pulmonary chondromas, or both, is unknown. By light microscopy, it has appeared to be of smooth-muscle derivation, and it has been interpreted as being epithelioid leiomyosarcoma. For further clues to its nature, we studied three examples by electron microscopy (two obtained from patients with extra-adrenal paragangliomas and one from a patient with pulmonary chondroma). Ultrastructurally, they were characterized by interdigitating cytoplasmic processes, plasma membrane-associated dense patches, an incomplete basement membrane, junctional complexes, randomly oriented filaments without periodicity, cytoplasmic dense bodies, pinocytotic vesicles, clustering of mitochondria, and rare cilia-features of normal smooth muscle or of smooth-muscle tumors with classic histologic patterns. Thus, the findings suggest that the three tumors we studied are of smooth-muscle derivation.

Clear cell sarcoma (CCS) is an uncommon, clinicopathologically distinct neoplasm that typically arises in association with tendons and aponeuroses. It shares several histologic and ultrastructural features with malignant melanoma. Clear cell sarcoma occasionally may be confused with other tumors of soft tissue that have a predominantly epithelioid appearance, including epithelioid leiomyosarcoma, epithelioid neurofibrosarcoma, synovial sarcoma, and epithelioid sarcoma. To assess the potential contribution of immunohistochemistry to this differential diagnosis, a panel of immunostains was applied to examples of each of these neoplasms. All six CCSs contained vimentin, and five were reactive with the melanoma-specific monoclonal antibody HMB-45. In addition, five CCSs expressed neuron-specific enolase, four cases displayed S100 protein, and four examples contained LN3 antigen. Synaptophysin and Leu-7 antigen were present in one case each. Cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, desmin, muscle-specific actin, and leukocyte common antigen were invariably absent. No other primary epithelioid neoplasm of soft tissue reacted with HMB-45. Clear cell sarcoma could be separated from epithelioid leiomyosarcoma by the presence of desmin and muscle-specific actin in the latter neoplasm. Similarly, both synovial sarcoma and epithelioid sarcoma differed from CCS by their expression of cytokeratin and epithelial membrane antigen. Clear cell sarcoma and malignant melanoma were immunohistochemically indistinguishable, supporting the concept that they share a common pattern of differentiation.

Angioendotheliomatosis is a rare, often disseminated proliferation of malignant intravascular cells of presumed endothelial origin. The disease may primarily affect the cerebral vasculature and lead to confusing symptoms and signs that often defy accurate clinical diagnosis.

An unusual case of localized cardiac amyloidosis was associated with sudden death in the absence of prior symptoms of heart disease. Autopsy studies showed amyloid deposition in the ventricular myocardium and conduction system; there were no deposits in other viscera, and evidence of a plasma cell dyscrasia was lacking. Thus, it appears that isolated involvement of the heart by amyloidosis may cause death, even in patients who do not have a history of congestive heart failure or arrhythmia.

In order to further define the pathobiologic changes that occur in Hashimoto's thyroiditis (HT) and Graves' disease (GD), 47 cases of these conditions and six of nodular thyroid hyperplasia were studied. Antibodies to cytokeratin, vimentin, LN-2 (a B-lymphocyte marker), UCHL-1 (a T-lymphocyte marker), and HLA-DR, and biotinylated Helix pomatia (Roman snail) lectin, were applied to paraffin sections using the avidin-biotin-peroxidase complex method. Cytokeratin was not expressed in resting epithelium or nodular hyperplasia, but was strongly displayed by injured (HT) or diffusely hyperplastic (GD) glandular tissue. Vimentin was present throughout the cytoplasm of proliferating thyrocytes but was limited to basal portions of resting cells and those of nodular hyperplasia. HLA-DR was observed in injured and hyperplastic thyroid tissue, as was N-acetyl-alpha-D-galactosamine, the target of H pomatia lectin. UCHL-1-labeled infiltrating lymphocytes were observed in both HT and GD, in areas with minimal epithelial changes, while LN-2 was observed only in association with well-formed lymphoid follicles. These findings suggest that T cells are implicated in the mechanism of both conditions, but that inflammation is not the initiating event for HT and GD; and that a "switch" in intermediate filament synthesis accompanies HLA-DR and N-acetyl-alpha-D-galactosamine expression by thyroid epithelium. Since current theories implicate intermediate filaments as intracellular mediators, we hypothesize that certain cytokeratins may be associated with gene activity governing the expression of class II histocompatibility antigens and other membrane glycoproteins in HT and GD.

Nephroblastomas (Wilms' tumors) from a dog, a bird, a pig, and a child were subjected to comparative immunocytochemical and lectin-histochemical analysis along with normal renal tissues from the same animals. Primary rabbit and mouse anti-human antibodies directed at intermediate-filament proteins, neuron-specific enolase, S100 protein, and epithelial membrane antigen were employed, as were biotinylated peanut agglutinin, soybean agglutinin, wheat germ agglutinin, and lectins from Dolichos biflorus and Ulex europaeus. The human neoplasm showed positivity for cytokeratin and epithelial membrane antigen and bound peanut, soybean, and wheat germ agglutinins in epithelial areas. Among the animal tumors, the porcine and canine nephroblastomas showed immunoreactivity for cytokeratin and vimentin in epithelial and blastematous areas, respectively. In addition, they were positive for S100 protein in epithelial foci. All of these results were substantiated by staining patterns in nonhuman kidneys. None of the neoplasms or renal tissues showed reactivity to the other antigens that were assessed. In the porcine tumor, endothelial cells bound D biflorus lectin, and epithelial areas were stained by U europaeus lectin. The avian nephroblastoma bound peanut, soybean, and wheat germ agglutinins, while the canine neoplasm showed no lectin-histochemical reactivity. These data appear to reflect limited immunohistological and histochemical similarities between nephroblastomas of different vertebrates.

The efficacy of two new monoclonal antibodies with cell lineage-restricted reactivity (HMB-45 [melanocytes] and anti-synaptophysin [neuroepithelial cells]) was compared with that of "traditional" antibody panels in the delineation of malignant melanoma (MM) of the sinonasal region, nasopharyngeal carcinoma (NPC), and olfactory neuroblastoma (ONBL). HMB-45 recognized all of eight melanomas and stained one of five neuroblastomas, but failed to label any of 12 cases of NPC. All examples of ONBL were stained by anti-synaptophysin; other tumors were nonreactive with this reagent. A panel of antibodies to cytokeratin, vimentin, epithelial membrane antigen, and S100 protein was also effective in discriminating between MM, NPC and ONBL. These results suggest that HMB-45 and anti-synaptophysin are comparable in utility to more extended antibody panels in the diagnosis of sinonasal malignancies, but only if used in combination with one another.

Antibodies to leukocyte common antigen (LCA) are valuable in surgical pathology in the diagnostic separation of malignant lymphomas from poorly differentiated neoplasms of other types. However, several publications have reported difficulty in obtaining adequate LCA labeling in paraffin-embedded specimens. To assess this problem further, we applied an amplified version of the avidin-biotin-peroxidase complex procedure to 315 formaldehyde-fixed hematopoietic malignancies, and 420 nonhematopoietic tumors that had been similarly processed. All non-Hodgkin's lymphomas were LCA-reactive with this method, whereas none of the nonhematopoietic neoplasms were stained. Twelve of 25 cases of Hodgkin's disease displayed LCA-positivity in Reed-Sternberg cells, but all contained reactive, benign inflammatory cells. Hence, the specificity of the amplified anti-LCA/avidin-biotin-peroxidase technique was 100%, and its sensitivity was 96%. This procedure should allow surgical pathologists to obtain reliable, reproducible staining of hematopoietic neoplasms in paraffin-embedded tissues.