Sub-lethal coral stress: detecting molecular responses of coral populations to environmental conditions over space and time.

In order for sessile organisms to survive environmental fluctuations and exposures to pollutants, molecular mechanisms (i.e. stress responses) are elicited. Previously, detrimental effects of natural and anthropogenic stressors on coral health could not be ascertained until significant physiological responses resulted in visible signs of stress (e.g. tissue necrosis, bleaching). In this study, a focused anthozoan holobiont microarray was used to detect early and sub-lethal effects of spatial and temporal environmental changes on gene expression patterns in the scleractinian coral, Montastraea cavernosa, on south Florida reefs. Although all colonies appeared healthy (i.e. no visible tissue necrosis or bleaching), corals were differentially physiologically compensating for exposure to stressors that varied over time. Corals near the Port of Miami inlet experienced significant changes in expression of stress responsive and symbiont (zooxanthella)-specific genes after periods of heavy precipitation. In contrast, coral populations did not demonstrate stress responses during periods of increased water temperature (up to 29°C). Specific acute and long-term localized responses to other stressors were also evident. A correlation between stress response genes and symbiont-specific genes was also observed, possibly indicating early processes involved in the maintenance or disruption of the coral-zooxanthella symbiosis. This is the first study to reveal spatially- and temporally-related variation in gene expression in response to different stressors of in situ coral populations, and demonstrates that microarray technology can be used to detect specific sub-lethal physiological responses to specific environmental conditions that are not visually detectable.

Erdheim-Chester disease: a histiocytic disorder more than skin deep.

Erdheim-Chester disease is a rare potentially malignant systemic non-Langerhans cell histiocytosis. Although classically described in the pulmonary system and long bones, cutaneous involvement has been chronicled in 2 previous case reports. Herein, we describe a single systemic case afflicting an elderly man with synchronous multifocal cutaneous disease. The previous literature and pertinent differential diagnosis will be discussed.

Primary cutaneous osteoblastic osteosarcoma: a case report and review of the current literature.

Osteosarcoma is a malignant bone-forming tumour that typically arises within the metaphysis of long bones. Extraskeletal osteosarcoma is a rare variant that usually arises in the deep soft tissues, especially in the legs. We report a 65-year-old white man with an ulcerated, nodular lesion of the forearm. Based on the histological features and immunohistochemical profile of the tumour, a diagnosis of osteoblastic osteosarcoma was made. Osteosarcoma arising in the skin is a rare condition that has seldom been reported in the English literature.

A surreptitious sinister sarcoma.

Angiosarcoma is an exceedingly rare endothelial-derived sarcoma that, when seen, usually presents as an expanding bruise-like patch or violaceous papule/nodule on the head of an elderly patient. Herein, we present the histologic features of an unusual case that defied initial diagnosis.

Dermal atypical lipomatous tumor/well-differentiated liposarcoma obfuscated by epidermal inclusion cyst: a wolf in sheep's clothing?

Epidermal inclusion cysts are an exceedingly common entity seldom seen in association with a malignant tumor. Herein, we report a unique case of an epithelial inclusion cyst seen in association with an atypical lipomatous tumor/well-differentiated liposarcoma. The epidermal inclusion cyst was delimited to the dermis and circumferentially enveloped by an atypical adipocyte tumor containing myxoid foci and comprised of lipoblasts. This case underscores the importance of scrutinizing the entirety of cysts and other ostensibly trivial dermal entities to avoid the pitfall of misdiagnosing a potentially serious tumor.

Benign lichenoid keratosis: a clinical and pathologic reappraisal of 1040 cases.

Benign lichenoid keratosis, otherwise known as lichen planus-like keratosis, is a common, cutaneous entity that is often confused with cutaneous malignancy. Few studies have examined the multiple clinical and pathologic guises of this entity, particularly within the context of clinical pathologic correlation or magnitude of this study. We examined the epidemiologic, clinical, and pathologic attributes of 1040 consecutive cases of benign lichenoid keratosis referred for pathologic examination at a busy laboratory over an entire year. Clinical parameters assessed included the age, anatomic location, gender, and multiplicity of the lesions. Pathologic attributes were assessed yielding discernment of five different subtypes that included a classic type, bullous type, atypical type with cytologically atypical lymphocytes, an early or interface type, and a late regressed or atrophic type. The results yielded an average age at presentation of 59.5 years with an age range of 36 to 87 years. The gender frequency was 76% female, 24% male. The trunk was the most common location (76%), followed by the extremities (33%) and head and neck (7%); 8% of patients presented with two lesions and less than 1% with three lesions prompting consideration of lichen planus. The classic, atypical, and bullous forms of the disease clinically presented with erythematous papule/plaque(s). The early or interface type showed erythematous to hyperpigmented brown macules and the regressed or atrophic type presented as violaceous papules or irregularly distributed macular pigmentation; 81% of the lesions showed the classic histology consisting of epidermal acanthosis with a band-like lichenoid lymphocytic infiltrate. Variable numbers of plasma cells, eosinophils, and neutrophils were identified as well as epidermal parakeratosis distinguishing these lesions from typical lichen planus. The bullous variant showed intraepidermal or subepidermal bullous cavities with a dense associated lymphocytic infiltrate and increased numbers of necrotic basilar layer keratinocytes. The atypical variant showed features of the classic type with scattered enlarged CD-3, CD-30 (+) lymphocytes possessing hyperchromatic, irregular nuclei. The early interface type showed single lymphocytes aligned along the dermoepidermal junction without epidermal acanthosis and adjacent lentigo. The regressed or atrophic variant showed epidermal atrophy with papillary dermal scarring, patchy lymphocytic infiltrates and melanin incontinence. The clinicopathologic spectrum of benign lichenoid keratosis is broad and encompasses several unrelated entities. An awareness of its expanded presentation is essential to avoid misdiagnosis and may serve as an important forerunner of pathogenic discernment.

Establishment and characterization of a new mantle cell lymphoma cell line, Mino.

Mantle cell lymphoma (MCL) is a distinct type of B-cell non-Hodgkin's lymphoma characterized by cyclin D1 overexpression and the cytogenetic abnormality, the t(11;14)(q13;q32). MCL cell lines have been difficult to establish and in vitro studies of these neoplasms are scarce. We describe the establishment and characteristics of a new MCL cell line, Mino. The cells are large, growing singly and in small clumps in vitro. By flow cytometry, the immunophenotype was compatible with MCL (i.e. CD5+CD20+CD23-FMC7+). Conventional cytogenetics showed hyperdiploidy with multiple complex karyotypic abnormalities, but no evidence of the t(11;14), proven to be present only by fluorescence in situ hybridization and polymerase chain reaction (PCR) methods. Western blots showed expression of cyclin D1 but no detectable cyclin D2 and cyclin D3; the retinoblastoma protein was predominantly phosphorylated. There was expression of tumor suppressor gene products including p53, p16(INK4a), and p21(WAF1). Sequencing of the TP53 gene revealed a mutation (codon 147(valine-->glycine)) in exon 5. Epstein Barr virus was absent. In summary, Mino is a new MCL cell line that may be useful to study the pathogenesis of MCL.

Cutaneous indeterminate cell histiocytosis: a new spindle cell variant resembling dendritic cell sarcoma.

BACKGROUND: Cutaneous indeterminate cell histiocytosis is a rare neoplastic disorder. Its varied histological presentation and rarity have limited efforts to determine its pathogenic relationship with other histiocytic lesions and possibly, its recognition. METHODS: We report on an unusual histologic pattern of indeterminate cell histiocytosis that resembled follicular dendritic sarcoma. A battery of immunohistochemical stains and electron microscopy were performed to elucidate the phenotype of the "histiocytic" cells. Based on a review of the literature, reported cases of indeterminate cell histiocytosis are presented and the diagnostic differential of spindle-cell lesions is discussed. RESULTS: Spindling histiocytes were positive for S-100 and CD1a. The monocytic/macrophage marker, CD68, and the dendritic cell marker, CD21, were negative. Electron microscopy failed to reveal Birbeck granules. CONCLUSIONS: Relatively few reports of indeterminate cell histiocytosis exist, some of which include discussion of potential overlaps with the non-X histiocytoses. Although the presence of prominent spindling in our case expanded the differential to include non-histiocytic disorders, the identified histiocytes unequivocally fulfilled the criteria of S-100 and CD1a positivity without demonstrable Birbeck granules.

Disseminated acanthamoebiasis presenting as lobular panniculitis with necrotizing vasculitis in a patient with AIDS.

BACKGROUND: Disseminated acanthamoebiasis is a rare entity, almost exclusively occurring in the immunocompromised host. METHODS: We report an unusual case of a 35-year-old female with recurrent sinusitis and multiple skin nodules demonstrating a necrotizing panniculitis, shown to be due to disseminated acanthamoebiasis. RESULTS: Histologic sections showed a neutrophilic lobular panniculitis with 20- to 30-microm trophozoites consistent with Acanthamoeba species. CONCLUSIONS: A review the literature shows that the histopathological presentation of acanthamoebiasis often eludes initial diagnostic attempts and that central nervous system (CNS) involvement is frequent and ultimately fatal. When amoebiasis is suspected, knowledge of the trophozoite and cyst forms may be helpful in distinguishing Acanthamoeba species from Entamoeba histolytica.

Assessing coral stress responses using molecular biomarkers of gene transcription.

We present a method for detecting rapid changes in coral gene expression at the messenger ribonucleic acid (mRNA) level. The staghorn coral Acropora cervicornis was exposed to 1 and 10 microg/L permethrin and 25 and 50 microg/L copper for 4 h. Using differential display polymerase chain reaction (PCR), mRNA associated with each toxicant exposure were reverse transcribed into complementary DNA (cDNA) fragments that were subsequently amplified and isolated. Six differentially expressed cDNA fragments were further developed into molecular probes that were used in Northern dot blots to determine the change in transcription levels of target transcripts. Changes in mRNA abundance were quantified by densitometry of chemiluminescence of digoxigenin-labeled probes hybridizing to target mRNA transcripts. The six gene probes showed varying degrees of sensitivity to the toxicants as well as specificity between toxicants. These probes were hybridized in Southern blots to genomic DNA from A. formosa sperm, which lacks zooxanthellae, to demonstrate that the genes coding for the mRNA transcripts produced are found within the coral genome. The gene probes developed in this study provide coral biologists with a new tool for coral assessment. Gene probes are sensitive, toxicant-specific biomarkers of coral stress responses with which gene sequence information can be obtained, providing a mechanism for identifying the stressor altering the gene expression.

Developing the Vascular Quality of Life Questionnaire: a new disease-specific quality of life measure for use in lower limb ischemia.

AIMS: The purpose of this study was to develop and validate an easily used disease-specific quality of life (QOL) measure for patients with chronic lower limb ischemia and to design an evaluative instrument, responsive to within-subject change, that adds to clinical measures of outcome when comparing treatment options in the management of lower limb ischemia. METHODS: The first phase consisted of item generation, item reduction, formulating, and pretesting in patients with ischemia. The proportion of patients who selected an item as troublesome and the mean importance they attached to it were combined to give a clinical impact factor. Items with the highest clinical impact factor were used to formulate a new 25-item questionnaire that was then pretested in 20 patients with lower limb ischemia. In the second phase, reliability, validity, and responsiveness of the new questionnaire were assessed in 39 patients with lower limb ischemia who were tested at 0 and 4 weeks. The King's College Hospital's Vascular Quality of Life Questionnaire and the Short-Form 36 were administered at each visit, and treadmill walking distance and ankle/brachial pressure indices were recorded. The new questionnaire's reliability, internal consistency, responsiveness, and validity were determined. RESULTS: Areas of QOL impairment were consistent through the ranges of disease severity and age, with no apparent differences between the men and women. Therefore, a single questionnaire is applicable to all patients with chronic lower limb ischemia. In stable patients test-retest scores demonstrated a reliability of r more than 0.90. Each item had internal consistency (item-domain Cronbach alpha =.7-.9). The questionnaire was responsive to change, with correlation between change in the questionnaire's total score and both global and clinical indicators of change (P <.001). The questionnaire showed face and construct validity. CONCLUSIONS: This disease-specific questionnaire is reliable, responsive, valid, and ready for use as an outcome measure in clinical trials. It is sensitive to the concerns of patients with lower limb ischemia, offering a simple method to measure the effect of interventions on their QOL.

Expression of the caveolins in dermal vascular tumors.

INTRODUCTION: Histopathologic criteria are usually sufficient for the accurate distinction of benign from malignant dermal vascular tumors. A minority of cases, however, pose a vexing diagnostic dilemma. Recent studies suggest that caveolin, a scaffolding cell membrane protein, may prove helpful in predicting the biologic behavior of endothelial-derived neoplasms. METHODS: We analyzed a series of 30 dermal vascular tumors including 12 lobular capillary hemangiomas (LCH), 4 cases of targetoid hemosiderotic hemangiomas (TH), 4 cases of tufted angioma (TA), 12 cases of Kaposi's sarcoma (KS), 4 epithelioid (EH) and 1 spindle cell hemangioendothelioma (SH), and 4 cases of angiosarcoma (AS). The distribution of immunoreactivity was analyzed by quantifying cell membrane staining in each case. RESULTS: There was a statistically significant difference in the expression of caveolin between LCH (mean labeling index=91.6), TH (mean labeling index=89.7), and TA (mean labeling index=87.2) and the cases of KS (mean labeling index=21.6, EH mean labeling index= 23.1), and the AS (mean labeling index=6.3). CONCLUSIONS: These results indicate that antibodies to caveolin may be useful in separating benign and malignant dermal vascular tumors and possibly implicates this peptide in their pathogenesis.

Cutaneous epithelioid malignant nerve sheath tumor with rhabdoid features: a histologic, immunohistochemical, and ultrastructural study of three cases.

INTRODUCTION: Malignant rhabdoid tumors are morphologically defined as sheets of loosely cohesive cells with eccentric nuclei and hyaline, paranuclear inclusions. Although originally described as a distinctive renal neoplasm of childhood, these tumors have since been described in all age groups and in a variety of extrarenal sites. In the latter setting, it is thought that the rhabdoid phenotype is comprised of histogenetically unrelated tumors, that regardless of histogenesis, pursue a biologically aggressive behavior. METHODS: We report on the clinical, histologic, immunophenotypic, and ultrastructural characteristics of three cases of cutaneous malignant rhabdoid tumor. RESULTS: Each of the cases arose on the trunk or the extremity of elderly men. None of the patients had neurofibromatosis. All of the lesions histologically showed sheets of loosely cohesive polygonal cells with eccentric nuclei and hyaline paranuclear inclusions. Each of the cases showed the following immunophenotype: S-100 (+), synaptophysin(+), vimentin (+), alpha smooth muscle actin (-), CD-30 (-), HMB-45 (-), and pankeratin(-). Ultrastructure of two of the cases yielded similar results showing paranuclear filamentous aggregates of intermediate filaments, cell membrane dense plaques, and rudimentary cell junctions consistent with nerve sheath differentiation. Tonofilaments, dense bodies, microtubules, neurosecretory granules, and melanosomes were not identified. Each of the patients died of widely metastatic disease within 1 year of diagnosis. CONCLUSIONS: Cutaneous epithelioid malignant nerve sheath tumor is a potentially aggressive tumor capable of showing rhabdoid differentiation thus simulating a variety of neoplasms. Immunophenotyping and ultrastructural analysis reliably discriminates these lesions from melanoma, de-differentiated carcinoma, lymphoma, and rhabdomyosarcoma.

Solitary fibrous tumors are immunophenotypically distinct from mesothelioma(s).

INTRODUCTION: Solitary fibrous tumor is a soft tissue tissue tumor of unknown histogenesis. Based upon histologic similarities and CD-34 expression, it has been suggested that these neoplasms bear some relationship to mesothelioma, and may represent its extra-pleural equivalent. METHODS: In order to further investigate this possible relationship, we examined a series of five dermal and five extra-cutaneous solitary fibrous tumors with antibodies directed against the mesothelial markers calretinin and HBME-1. RESULTS: All the lesions failed to stain with the antibodies tested. This suggests that despite some similar histologic and immunophenotypic features, these lesions are not immunophenotypically identical. Mesotheliomas are CD-34(+), calretinin(+), HBME-1(+), while solitary fibrous tumors are CD-34(+), calretinin(-), HBME-1(-). CONCLUSIONS: The histogenesis of solitary fibrous tumor remains elusive. It is unlikely that tumor location or tumor de-differentiation accounts for the dichotomous staining properties, as these neoplasms show a similarly benign histologic appearance regardless of location.

Elastofibroma of the foot: uncommon presentation: a case report and review of the literature.

We report the clinical, microscopic and ultrastructural features of an elastofibroma arising in the foot. The lesion typically occurs in the elderly, and in 85% of cases arises from the connective tissue of the posterior chest wall. The histopathologic features of this lesion are distinctive, and are characterized by a haphazard array of eosinophilic collagen and elastic fibers, associated with fibroblasts and aggregates of mature fat cells. There are only two reported cases in the literature arising in the foot.

Pigmented squamous cell carcinoma of the skin: morphologic and immunohistochemical study of five cases.

Invasive pigmented squamous cell carcinoma (PSCC) of the skin is reportedly rare. Herein, we evaluate an additional five cases and compare their relative frequency with non-pigmented squamous cell carcinoma (SCC). Of 46,791 archived cases of SCC, a total of five cases of PSCC were discovered for a relative frequency of approximately 0.01%. Grossly, each tumor presented as a rapidly growing crusted papule on actinic damaged skin of the face. Microscopically, all were composed of a mixture of keratininized squamous cells and melanin-producing dendritic melanocytes. The squamous cells stained for epithelial membrane antigen, and both low and high molecular keratins. The melanocytes stained for S-100 and HMB-45. A matched series of 31 SCCs were subjected to an identical immunohistochemical battery of stains to determine if a histologically subtle and unsuspected number of intratumoral melanocytes existed in SCC. Each of the cases failed to show intratumoral melanocytes. The differential diagnosis and possible histogenesis of PSCC is discussed and the importance of extensive pathologic examination to prevent misdiagnosis is emphasized. Despite the histologic dissimilarity, the long-term prognosis of the reported cases was similar to conventional SCC.