The depth of follicular extension in actinic keratosis correlates with the depth of invasion in squamous cell carcinoma: implication for clinical treatment.

BACKGROUND: Actinic keratosis (AK) may show extension down follicles, not only in cases with full-thickness epidermal atypia ('bowenoid' AK), but also in cases with atypia limited to the epidermal basalis. Previous studies have demonstrated that, in bowenoid AK, follicular extension is usually superficial, being limited to the upper follicular segment. Little is known about the depth of follicular involvement in cases of invasive squamous cell carcinoma of the skin (iSCC) arising from AK and the role of the follicle in iSCC pathogenesis. OBJECTIVE: This study investigated the relationship between follicular extension of atypical keratinocytes in an AK and the development of iSCC from the follicular wall. The depth of follicular extension was correlated with the depth invasion of iSCC. Differences between the differentiated and classical pathways of iSCC were also examined. METHODS: We performed a retrospective histologic review of 193 biopsy specimens of iSCC with an associated AK. We assessed the presence and depth of follicular extension of atypical keratinocytes in the AK, using tumour (Breslow) thickness and the follicular unit level (infundibular, isthmic and subisthmic), as well as iSCC being present directly adjacent to the follicular basalis. RESULTS: Follicular extension was present in 25.9% of the cases (50 cases), usually extending into the lower follicular segment. The iSCC was present directly adjacent to the follicular basalis in 58% of the cases (29 cases), correlating highly with the depth of follicular extension (infundibular: 3/12; isthmic: 21/33; subisthmic 5/5). CONCLUSION: The depth of follicular extension of atypical keratinocytes in an AK correlates with the development of depth of invasion of an associated iSCC, irrespective of the pathway of origin. It is therefore important to note the presence and the depth of follicular extension when diagnosing an AK, as follicular extension likely accounts for a significant proportion of recurrent AK and the development of iSCC following superficial treatment modalities.

Comparative genomic hybridization in the detection of DNA copy number abnormalities in uveal melanoma.

Genomic instability appears to play an important role in the development, growth, invasiveness, and eventual metastasis of the neoplastic cell. We have used a powerful new technique, comparative genomic hybridization, to evaluate genetic alterations in 10 fresh frozen uveal melanomas. Comparative genomic hybridization utilizes dual fluorescence in situ hybridization to characterize chromosome deletions and duplications, allowing for simultaneous evaluation of the entire human genome. Several consistent chromosomal abnormalities were detected. This study confirmed previous findings obtained using standard cytogenetic techniques but demonstrated an increased incidence in abnormalities of chromosomes 3 and 8; there was loss of chromosome 3 and duplication of 8q. In addition, we identified, although less frequently, other recurrent abnormal regions including alterations on chromosomes 6p, 7q, 9p, and 13q.

The histopathology of cutaneous lesions of Kikuchi's disease (necrotizing lymphadenitis): a report of five cases.

Kikuchi's disease (KD) is an idiopathic, self-limited necrotizing lymphadenitis that can clinically and histologically mimic high-grade lymphoma, including Hodgkin's disease, or can be mistaken for the lymphadenitis of systemic lupus erythematosus (SLE). Involvement of extranodal sites is unusual but well documented, especially in Asia, where KD is more common than in North America or Europe. The successful distinction of KD from malignant lymphoma and SLE is imperative for the appropriate treatment of affected patients. We describe five patients with cutaneous involvement by KD, all of whom presented with fever, lymphadenopathy, and an eruption on the skin of the upper body, which in one case was clinically suspected to be due to SLE and in another, polymorphous light eruption. The patients ranged in age from 10 months to 42 years (median, 33 years) and included three females and two males. All five patients had negative serologic studies for collagen vascular disease. Each patient had a lymph node biopsy showing the typical necrotizing lymphadenitis of KD. Skin biopsies from all five patients shared a specific constellation of histologic features: vacuolar interface change with necrotic keratinocytes, a dense lymphohistiocytic superficial and deep perivascular and interstitial infiltrate, varying amounts of papillary dermal edema, and abundant karyorrhectic debris with a conspicuous absence of neutrophils and a paucity of plasma cells, paralleling the nodal histology in KD. CD68 immunohistochemistry on paraffin-embedded sections showed many histiocytes and plasmacytoid monocytes in all cases, whereas CD3, CD4, and CD8 showed highly variable staining among the cases. There was only rare staining with TIA-1 and CD30. We believe that the papular eruption of KD has recognizable histopathologic features and that a CD68 stain that marks many cells that initially seem to be lymphocytes can be performed to confirm the diagnosis.

Molecular cytometry of cancer.

The application of molecular probes to diagnosis and prognosis of malignancies has redefined our perceptions of disease, allowing diagnosis by genotypic rather than phenotypic criteria. DNA analysis is especially useful when applied to pathological material in situ, because this allows the pathologist to combine information from both morphological and molecular observations. DNA in situ hybridization is a useful approach for the molecular pathologist, especially when combined with cytometric analysis. Potential clinical applications for in situ hybridization and the recently described technique of comparative genomic hybridization in tumor diagnosis and prognosis are described.

Preoperative ultrasound and thallium-technetium subtraction scintigraphy in localizing parathyroid lesions in patients with hyperparathyroidism.

Clinical and biochemical evaluation of patients with hypercalcemia are today extremely accurate in identifying those with primary hyperparathyroidism. Neck exploration by an experienced parathyroid surgeon is equally likely to identify correctly the diseased gland or glands. It has been suggested that recently devised localization techniques may allow the surgeon to limit the extent of the procedure to one side of the neck. The present retrospective study was undertaken to determine the reliability with which two such imaging procedures, ultrasonography (US) and thallium-technetium subtraction scanning (TTSS) localize these lesions by specific site or side. The identity of each patient undergoing parathyroidectomy at a metropolitan medical center was determined by review of the operating room log. From the records of each subject were noted the results of any imaging studies done, the location of lesions found at surgery, and the histologic diagnosis. Accuracy and positive predictive value of US and TTSS were then calculated on the basis of precise and lateralizing localization. Seventy-four patients underwent primary neck exploration during the study period. In 69 patients US, TTSS, or both were performed preoperatively, and among these, data were complete in 65. Ultrasound correctly localized the site of a lesion in 31 of 63 subjects, and TTSS in 25 of 45. Ultrasound correctly localized the side on which the lesion lay in 35 of 62 subjects, and TTSS in 27 of 45. In 29 of 42, one or both studies correctly identified the side on which the lesion lay. In only one of 13 subjects with hyperplasia were all four glands correctly identified as hyperplastic.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary alveolar proteinosis: a pediatric case study.

Pulmonary alveolar proteinosis (PAP) is a rare, debilitating, sometimes fatal disease of uncertain etiology and pathophysiology. The medical literature defines the illness and describes current theories related to its pathophysiology. Little nursing literature addresses PAP. This case study describes and discusses nursing interventions utilized in the home management of a young, female adolescent with this illness. A retrospective analysis of the chart reveals investigative treatment involving daily subcutaneous injections of bacterially synthesized, granulocyte-macrophage colony-stimulating factor. Communication and collaboration among health care providers and identification of diverse issues influencing the health of the client resulted in the development of effective nursing interventions. Leininger's Theory of Transcultural Care Diversity and Universality provides a model for interpretation and generalization of nursing interventions. PAP can be managed successfully in the home, but more information on the illness and ethnic and age-specific responses to treatment is needed.

Cytogenetics of cutaneous malignant melanoma.

Numerous chromosomal aberrations have been identified by karyotyping cell lines of malignant melanoma. The author discusses specific recurrent aberrations, patterns of familial occurrence, and frontiers for future research.

Quantitation of total DNA per cell in an exponentially growing population using the diphenylamine reaction and flow cytometry.

The diphenylamine assay used to estimate the absolute mass of DNA/cell as well as absolute differences in DNA content between cell populations is based upon the assumption that all of the cells are in the G0 or G1 phase of the DNA synthetic cycle. However, if cells are in exponential growth and synthesizing DNA, portions of the population will be in S or G2 phases and the diphenylamine assay will overestimate the total mass of DNA/cell. Conversely, flow cytometry (FCM) can estimate relative differences in total DNA/cell and the proportions of an exponentially growing population in G1, S, and G2 but cannot estimate absolute mass or differences in DNA/cell. In this report, we describe a methodology of combined diphenylamine and FCM assays of total DNA/cell which is applicable to any eukaryotic cell population. The method involves using the two assay methods concurrently and correcting the diphenylamine data for the FCM-derived distribution of the cells within the DNA synthetic cycle. The methodology was tested on single-cell-derived stocks of the obligate intracellular protozoan parasite Trypanosoma cruzi which displays marked but stable intraspecific heterogeneity.

Cytogenetic profiling using fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH).

Fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) allow cytogenetic analyses of primary tumors without culture. CGH allows detection and mapping of allelic imbalance by simultaneous in situ hybridization of differentially labeled tumor (green fluorescing) and normal DNA (red fluorescing) to a normal human metaphase spread. Regions of increased or decreased copy number in the tumor are mapped onto the normal metaphase chromosomes as increases or decreases in the green to red fluorescence ratio. This technique gives a comprehensive assessment of gene dosage imbalance throughout the tumor. However, it is limited, at present, to fairly large tumors containing few normal cells. FISH, on the other hand, allows analysis of DNA sequence copy number at specific loci in single nuclei. A wide variety of DNA probes is available for FISH, including chromosome-specific probes which hybridize to alpha-satellite pericentromeric DNA regions (to detect changes in specific chromosome copy number and overall ploidy) and specific locus probes targeting 20-150 kilobase sequences (to detect specific amplifications, deletions, breakpoints, or rearrangements). FISH using these probes has been applied to interphase nuclei in touch preparations, smears from fine needle aspirates, and thin (< 6 microns) and thick (> 20 microns) sections cut from formalin-fixed, paraffin-embedded tissue. Analysis of thick sections allows accurate actual signal enumeration within the histological context. This approach may allow analysis of subtle premalignant, early malignant, and infiltrating tumors in which malignant cells must be differentiated from nonmalignant cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Thick-section fluorescence in situ hybridization on formalin-fixed, paraffin-embedded archival tissue provides a histogenetic profile.

Fluorescence in situ hybridization has become a major tool for analysis of gene and chromosome copy number in normal and malignant tissue. The technique has been applied widely to fresh tissue and dispersed formalin-fixed, paraffin-embedded archival tissue, but its use on sections of archival tissue has largely been limited to sections < 6 mu thick. This does not provide intact, uncut nuclei for accurate analysis of gene or chromosome copy number. We report here a method of hybridization to sections > 20 microns thick that overcomes these difficulties. Key developments were the use of DNA probes directly labeled with fluorochromes and optical sectioning using laser-scanning confocal microscopy.

Efficient, interactive, and three-dimensional segmentation of cell nuclei in thick tissue sections.

Segmentation of intact cell nuclei in three-dimensional (3D) images of thick tissue sections is an important basic capability necessary for many biological research studies. Because automatic algorithms do not correctly segment all nuclei in tissue sections, interactive algorithms may be preferable for some applications. Existing interactive segmentation algorithms require the analyst to draw a border around the nucleus under consideration in all successive two-dimensional (2D) planes of the 3D image. The present paper describes an algorithm with two main advantages over the existing method. First, the analyst draws borders only in 2D planes that cut approximately through the center of the nucleus under consideration so that the nuclear borders generally are most distinct. Second, the analyst draws only five borders around each nucleus, and then the algorithm interpolates the entire surface. The algorithm results in segmented objects that correspond to individual, visually identifiable nuclei. The segmented surfaces, however, may not exactly represent the true nuclear surface. An optional, automatic surface optimization algorithm can be applied to reduce this error.

Community hospital level II trauma center outcome.

Currently, level II trauma center standards allow trauma surgeons to take call out-of-hospital. To address the concern that this practice may adversely influence outcome, we tested the hypothesis that the survival of injury victims treated at a level II trauma center is significantly different from that predicted by the Major Trauma Outcome Study (MTOS). In addition, we examined the impact of trauma surgeons taking call out-of-hospital on the survival of patients with severe thoracoabdominal injury. Over a 26-month period, a total of 3,689 consecutive injured patients who were treated at a community hospital level II trauma center were entered into this study. There was no significant difference between the MTOS survival and the actual survival in the overall population (96% vs. 97%, respectively; Z statistic = ns). Among the patients with severe thoracoabdominal injury (i.e., Abbreviated Injury Scale score greater than or equal to 3), there was no significant difference in survival between the patients whose arrival time corresponded to the presence of an in-hospital surgeon (0700-1800 hours) versus those who arrived when a surgeon was generally out-of-hospital (1801-0659 hours), (76% vs. 81%, respectively; p = ns). From these data we conclude that there was no significant difference between the survival observed and that predicted by the MTOS at our community hospital, which complies with level II trauma center standards. Furthermore, in the cohort with severe thoracoabdominal injury, the response of trauma surgeons from out-of-hospital did not adversely influence survival.

Selective use of computed tomography and diagnostic peritoneal lavage in blunt abdominal trauma.

The purpose of this study was to attempt to identify those blunt trauma patients in whom expensive diagnostic studies such as computed tomography and diagnostic peritoneal lavage are unnecessary to exclude intra-abdominal injury. The medical records of 1096 blunt trauma patients evaluated at an urban level I trauma center were reviewed. Because of the urgent need to exclude intra-abdominal hemorrhage in patients with hypotension (blood pressure < 90 mm Hg), and the difficulty in obtaining reliable information from abdominal examination in patients with Glasgow Coma Scale scores < 11 or spinal cord injury, 140 patients meeting these criteria were reviewed but excluded from statistical analysis. Six groups of major associated injuries felt to be potential risk factors for the prediction of intra-abdominal injury were analyzed in the 956 remaining patients. Only two of these potential risk factors, namely chest injury (p = 0.0001) and gross hematuria (p = 0.0003) attained statistical significance. All of the 44 significant intra-abdominal injuries occurred in the group of 253 patients that had either an abnormal abdominal examination, one of the statistically significant risk factors, or both, for a sensitivity of 100%. Of the 703 patients with a normal abdominal examination and no risk factors, none had a significant abdominal injury, for a negative predictive value of 100%. This study suggests that patients with either an abnormal abdominal examination or one of the two statistically derived risk factors require adjunctive diagnostic evaluation with diagnostic peritoneal lavage or computed tomography scan to exclude intra-abdominal injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Cutaneous Waldenstrom macroglobulinemia in transformation.

Waldenstrom macroglobulinemia is a low-grade B-cell lymphoproliferative disorder of the elderly with characteristic monoclonal IgM-producing neoplastic infiltrates of the bone marrow, lymph node, and spleen. Cutaneous manifestations are usually nonspecific such as purpura, ulcers, and urticarial lesions. These lesions are caused by hyperviscosity of the blood, immune complex-mediated vascular damage, paraprotein deposition, and amyloid deposition. Specific skin lesions occur rarely and generally consist of translucent, flesh-colored papules composed of monoclonal IgM deposits. Rarely, there may be violaceous lesions composed of low-grade lymphoplasmacytic infiltrates characteristic of Waldenstrom macroglobulinemia. Both cutaneous manifestations of the disease, as well as disease transformation to high-grade, large cell lymphoma are rare. We report two very unusual cases of Waldenstrom macroglobulinemia with documented skin disease that demonstrated transformation to high-grade lymphoma. Both patients were elderly men with long-standing Waldenstrom macroglobulinemia involving the bone marrow, who subsequently developed skin involvement by the disease. Waldenstrom macroglobulinemia can rarely manifest as cutaneous disease, sometimes as a high-grade transformation of low-grade Waldenstrom macroglobulinemia elsewhere. Distinction of cases of transformed Waldenstrom macroglobulinemia from de novo cutaneous large cell lymphoma may be important, because the two entities are likely biologically different.