Biomedical subjects
Publications and source records attributed to L Barnes.
We describe a 9-year-old boy with an Ro-positive, subacute, cutaneous lupus rash associated with homozygous C2 deficiency. His response to a mild topical steroid and sunscreen was excellent. Hereditary complement deficiency and its association with childhood lupus erythematosus are discussed.
Paraganglioma and atypical carcinoid tumor of the larynx are two neuroendocrine neoplasms that have often been confused in the past, and even in the present, in the literature. The clinicopathological profile of the two lesions is presented and the differential diagnosis is discussed. A correct diagnosis is of paramount importance, since treatment and prognosis depend on diagnostic accuracy and differ for the two lesions. Paraganglioma of the larynx is usually benign, whereas atypical carcinoid tumor is malignant and has an aggressive clinical course.
A retrospective analysis of formalin-fixed, paraffin-embedded tissue from patients with histologically confirmed metastatic squamous cell carcinoma was performed using flow cytometry. Ninety-eight sets of specimens from previously untreated patients with an oral cavity or oropharyngeal tumor and a simultaneous cervical metastatic deposit were analyzed. Normal mucosa and cervical lymph nodes were processed identically and run as controls. All patients underwent surgical resection at Wilford Hall USAF Medical Center or The Eye and Ear Hospital of Pittsburgh between 1980 and 1986. The specimens from 94 patients were technically adequate for interpretation. Diploid histograms in both the primary and metastatic tumors were present in 49 (52%) of 94 patients. Aneuploid histograms in either the primary and metastatic tumors were noted in 45 (47%) of 94 patients. In this group of 45 patients, the primary tumor and cervical metastasis were both aneuploid in 21 (46%), and aneuploid histograms occurred with equal incidence in either the primary or metastasis in the remaining 24 cases. No statistically significant prediction of survival could be made from any correlation with the histograms of either the primary or metastasis. The potential technical problems and limitations of flow cytometry in the determination of DNA content of formalin-fixed, paraffin-embedded tissue and the selection of patients with advanced disease warrant caution in the interpretation of results.
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The biologic behavior of invasive pituitary adenomas is poorly understood and appears to be intermediate between intrasellar adenomas and pituitary carcinoma. Utilizing immunohistochemistry on tissue sections, we examined 10 invasive pituitary adenomas involving the sphenoid sinus with a panel of cellular and molecular markers and compared the results with 10 noninvasive pituitary adenomas and five normal pituitary glands. The panel included Ki-67 and PCNA (proliferation cell nuclear antigen), cell proliferation indicators; interleukin 6 (IL-6), a multifunctional cytokine; heat shock protein 27 (HSP 27), a stress response protein; and p53, a tumor suppressor gene product. We found strong expression of IL-6 in normal pituitary glands, 20% of noninvasive and 50% of invasive adenomas. HSP 27 was absent in normal glands and present in 10% of noninvasive and 50% of invasive adenomas. The Ki-67 and PCNA proliferation index was above normal but was essentially the same in the two groups. p53 was not detected in any specimens. We propose that both IL-6 and HSP 27 may be markers of biologic aggression in pituitary adenomas.
We describe two cases of basaloid squamous cell carcinoma of the head and neck with a spindle cell component. One tumor arose from the tonsil and the other in the larynx. Of the 30 cases of basaloid squamous cell carcinoma seen at this medical center, only 2 (6.6%) have demonstrated this histologic feature. To our knowledge, scant information exists with regards to a prominent spindle cell component occurring in basaloid squamous cell carcinoma, and none has been officially documented.
This paper describes the pathobiology of some of the more common skull base tumors. In addition to clinicopathologic features, emphasis is placed upon methods of diagnosis utilizing immunoperoxidase stains and molecular markers that may or may not impact upon prognosis.
Salivary duct carcinoma is an uncommon and relatively unknown clinically aggressive adenocarcinoma of salivary origin that histologically demonstrates a remarkable resemblance to invasive carcinoma of the breast. We report the clinicopathologic features of 13 cases that were also examined by image analysis for DNA ploidy. The results were then analyzed collectively with the less than 100 cases of salivary duct carcinoma reported in the English-language literature to define the characteristics of this unusual neoplasm. The 12 men and one woman averaged 68 years of age (range, 49 to 90 years). All tumors arose in the parotid (10 cases) or submandibular glands (three cases). Nine tumors were aneuploid, three diploid, and one was indeterminate because of insufficient tissue. Follow-up (median, 24 months) was available in 12 cases: three patients died of disease, six were alive without disease, and three died of other causes. Combining our cases with those in the literature, a total of 104 cases, confirms that salivary duct carcinoma is a highly malignant neoplasm with distinctive clinical and pathologic features. It arises almost exclusively in the major salivary glands (96% of cases), is three times more common in men, and usually occurs in patients over 50 years of age (range, 22 to 91 years). One-third of patients experience local recurrences, 59% develop positive regional lymph nodes, 46% have systemic metastases (lungs and bones), and 65% die of their disease, usually within 4 years of diagnosis. Determination of tumor ploidy has no prognostic significance. The presence of distant metastasis was the only clinicopathologic feature that was statistically associated with prognosis (p = 0.02); all patients with systemic metastasis died of disease.
Salivary duct carcinoma is an infrequent highly aggressive salivary gland tumor that is histologically similar to ductal carcinoma of the breast. We studied 13 cases by immunohistochemistry for the presence of estrogen and progesterone receptors, cathepsin D, and c-erbB-2 protein to determine whether the similarity to breast carcinoma extended beyond the light microscope to the molecular level and, if so, whether these markers might have therapeutic or prognostic value. Twelve of 13 cases contained sufficient amounts of tumor tissue for evaluation. Of these 12 cases, one (8%) was positive for estrogen receptors, none was positive for progesterone receptors, five (42%) were positive for cathepsin D, and three (25%) were positive for c-erbB-2 protein. Expression of cathepsin D and c-erbB-2 protein does not appear to have prognostic significance in salivary duct carcinoma. The 8% incidence of immunopositivity for estrogen receptors and absence of progesterone receptors in salivary duct carcinoma is considerably less than that seen in breast cancer. Nevertheless, because the occurrence of systemic metastasis in salivary duct carcinoma is such an ominous development largely unresponsive to chemotherapy, antihormonal therapy, such as used in breast cancer, might be considered on a trial basis for those tumors that are estrogen receptor-positive when conventional therapeutic modalities fail.
OBJECTIVES: To examine the immunohistological features in the involved skin of patients with psoriatic arthritis (PA) (n = 15), compared with those in involved skin from patients with psoriasis but no arthritis (n = 5), and with a group with normal skin (n = 4), to identify markers for arthritis in psoriasis. METHODS: Skin was obtained from patients by 6 mm punch biopsy and normal skin was provided by the department of plastic surgery. Samples were stained with monoclonal antibodies against T cells (CD3, CD8, CD4, CD45Ro), B cells (CD20), macrophages (mac387), vascular endothelium (FVIII-related antigen) and a Langerhan's cell marker (p155). The number of cells/vessels staining with each monoclonal antibody was calculated and serial sections of skin were examined to estimate the presence of DR+ keratinocytes. RESULTS: There were significantly more CD45Ro T-cells and blood vessels in patients with psoriatic arthritis compared with both psoriasis alone, and with normal controls (p < 0.02). While B-cells were not seen in psoriasis without arthritis or in normal skin, a small but significant number were observed in PA (p < 0.02). Furthermore, while DR+ keratinocytes were present in both psoriatic arthritis and psoriasis skin, there were significantly more DR+ cells in the psoriatic arthritis epidermis compared with psoriasis alone (p < 0.02). CONCLUSIONS: This study suggests that increased numbers of CD45Ro T-cells, greater vascularity, the presence of B-cells, and increased numbers of DR+ epidermal cells are markers for arthritis in patients with psoriasis.
This study details the clinicopathologic features of 62 cases of laryngeal paraganglioma (LP), including 54 acceptable cases identified in the literature (although clinical information is lacking on 7 of these) and 8 previously unpublished cases identified from the Registry of Otolaryngic-Endocrine Pathology at the Armed Forces Institute of Pathology. Demographic findings show that the overwhelming majority of cases affect women (41:14), mainly in the fourth to sixth decades of life (age range, 14 to 83 years; median, 44 years), with a prevalence in the supraglottic larynx. These neoplasms are treated by surgical resection and are benign. Despite the characteristic pathologic features associated with LP, it is sometimes confused with other neoplasms, particularly neuroendocrine carcinomas of the larynx, and this confusion leads to unfortunate designations such as malignant paraganglioma and metastasizing paraganglioma of the larynx. Judging from the cases reported in this study and those identified in the literature, we conclude that malignant biologic behavior associated with LP is extraordinarily rare (< 2%). Because of the misdiagnoses of LP, the prognosis associated with this entity has been skewed to suggest that LP may behave aggressively. This has led to the inappropriate classification of LP among the malignant categories of laryngeal neuroendocrine neoplasms. The goal of this study is to detail the features diagnostic of LP and to discuss the appropriate treatment, prognosis, and classification of these neoplasms.
BACKGROUND: The lung injury in adult respiratory distress syndrome (ARDS) has been associated with increased expiratory hydrogen peroxide (H2O2) concentrations. Furthermore, patients with sepsis and ARDS are reported to have greater serum scavenging of H2O2 than patients with ARDS only. We hypothesized that the systemic presence of H2O2 would be detectable in the urine of these two groups of patients and that, in the case of ARDS sepsis, the relative contribution of each disease to the production this analyte would be discernible. Accordingly, we used an in vitro radioisotope assay to follow the weekly course of urine H2O2 levels in ARDS patients with and without sepsis, and in samples from control non-ARDS patients with sepsis with indwelling urinary catheters and in samples provided by healthy volunteers. METHODS: Thirty patients with ARDS were included in the study: 23 had sepsis and 7 were sepsis free. An indwelling catheter was used to collect urine from each patient over a 24-h period, first within 48 h of ICU admission and then every seventh day over the course of their illness. Urine H2O2 was measured by competitive decarboxylation of 1-14C-alpha-ketoglutaric acid by H2O2. Urine samples were provided by 20 healthy volunteers while, in 10 non-ARDS patients with sepsis, urine was collected over one 24-h period following a 5-day minimum with an indwelling urinary catheter. RESULTS: Urine H2O2 concentration in healthy control subjects (88 +/- 4 mumol/L) and non-ARDS patients with urinary catheters (96 +/- 5 mumol/L) was not significantly different. During the first 48 h in the ICU, urine H2O2 in patients with ARDS only (295 +/- 29 mumol/L) was significantly lower (p < 0.05) than patients with ARDS and sepsis (380 +/- 13 mumol/L); however, the lung injury scores of these two groups did not differ. Furthermore, within the first 48 h, the urine H2O2 of the patients with ARDS and sepsis who did not survive (427 +/- 19 mumol/L; n = 7) was significantly higher than that in patients who survived sepsis (352 +/- 14 mumol/L; n = 15). Thereafter, the lung injury scores and urine H2O2 levels of the nonsurvivor ARDS-sepsis group remained significantly higher compared with the other two groups. At lung injury scores of 3 and 2, regardless of days in ICU, the patients with ARDS only had significantly lower urine H2O2 (266 +/- 30 mumol/L and 167 +/- 24 mumol/L, respectively) compared with the survivor ARDS-sepsis group (376 +/- 19 mumol/L and 250 +/- mumol/L). When the patients with ARDS (both ARDS only and with sepsis) recovered, their urine H2O2 concentration did not differ from the control groups (healthy donors and patients without ARDS). CONCLUSION: Lung injury scores did not differentiate patients with ARDS and sepsis from patients with ARDS only during the first 10 days in the ICU; however, urine H2O2 levels were significantly greater in the patients with ARDS and sepsis. Moreover, despite no initial difference in lung injury, patients who did not survive ARDS and sepsis had consistently greater urine H2O2 concentration than patients who survived sepsis. The urine H2O2 level in the ARDS-only group was about 70 percent of the level in the survivor ARDS and sepsis group, suggesting that ARDS alone is the major contributor to the H2O2 oxidant processes during combined ARDS and sepsis. Furthermore, these studies demonstrate that urine H2O2 may be a useful analyte to differentiate the severity of oxidant processes in patients with ARDS and sepsis albeit the prognosis appears to be survival or nonsurvival.
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Interleukin 2 (IL2) was injected peritumorally and intranodally in 36 patients with unresectable squamous cell carcinoma of the head and neck enrolled in an Eastern Cooperative Oncology Group-sponsored phase Ib trial (EST P-Z388). Groups of 6 patients received escalating doses(200, 2 x 10(3), 2 x 10(4), 2 x 10(5), 2 x 10(6), and 4 x 10(6) units) of IL2 daily 5 times/week for 2 weeks. Tumor biopsies were obtained before and after IL2 therapy. Tumor tissue was provided for histology, and the remaining fresh tissue was divided for snap-freezing in -75 degrees C and for separation of tumor-infiltrating lymphocytes (TIL) and tumor cells. Immunophenotyping of TIL performed on cryostat sections of paired pre- and post-IL2 biopsy tissues showed increases after IL2 therapy in the number of T-cells (P = 0.005), natural killer (NK; CD16+) cells (P = 0.0001), CD25+ cells (P = 0.004), and HLA-DR+ cells (P = 0.001) accumulating in the tumor stroma. In the tumor parenchyma, NK cells (P = 0.0001) and HLA-DR+ cells (P = 0.003) were increased after IL2 therapy. The T:NK cell ratios in the tumor stroma and parenchyma were decreased after therapy, suggesting selective accumulation of NK cells. By flow cytometry, TIL recovered from post-IL2 biopsy tissues were enriched (P < 0.05) in CD3-CD56+ (NK) cells. In situ hybridization with [35S] cDNA probes for cytokines and IL2 receptors indicated that the numbers of cells expressing mRNA for IL2, tumor necrosis factor alpha, IL1-beta, gamma-interferon, transforming growth factor beta, and IL2 receptor p55 or p70 were increased in post-IL2 biopsy tissues as compared to pre-IL2 tissues. Cytolytic activity of TIL isolated from post-IL2 tissues was also increased, as determined in 4-h 51Cr release assays against K562 targets (12 +/- 3 mean lytic units/10(7) cells +/- SEM pre-IL2 versus 46 +/- 13 post-IL2; n = 16) and against autologous tumor (13 +/- 8 versus 68 +/- 26; n = 9). Fresh TIL of one clinical responder showed relatively high levels (195 lytic units) of autotumor cytotoxicity after IL2 therapy versus no activity prior to therapy. In the blood, NK and lymphokine-activated killer cell activity, and percentages of CD3-CD56+ NK cells and of activated (CD25+) T-lymphocytes were increased for all doses of IL2.(ABSTRACT TRUNCATED AT 400 WORDS)
OBJECTIVE: To define the immunohistologic features of the synovial membrane (SM) of patients with psoriatic arthritis (PA) and to compare them with those of an age- and disease-duration-matched population of patients with rheumatoid arthritis (RA). METHODS: Synovial membrane needle biopsy was performed on 15 PA patients with knee involvement (8 had asymmetric oligoarthritis and 7 had symmetric polyarthritis) and on 15 RA controls. Specimens were stained with monoclonal antibodies against T cells (CD3, CD8, CD4, CD45RO), B cells (CD20), macrophages (Mac387, CD14), and cells bearing class II antigens (DAKO-DR). Vascular endothelium was examined using a polyclonal antibody to Factor VIII-related antigen, and adhesion molecule expression was examined using antibodies 1.3B6, 6.5B5, and 1.4C3, which identify endothelial leukocyte adhesion molecule 1 (ELAM-1), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1), respectively. RESULTS: There was significantly less lining layer hyperplasia, fewer macrophages, and a greater number of blood vessels in PA SM than in RA SM: ELAM-1 expression was less intense in PA than in RA SM, while there was no difference in expression of ICAM-1 and VCAM-1. Numbers of B cells, T cells, and T cell subsets (predominantly CD4, CD45RO T cells) were similar in both groups of patients. CONCLUSION: Our findings demonstrate important differences in the immunohistologic features of PA and RA SM: The PA SM is more vascular, ELAM-1 expression is less intense, and fewer macrophages invade the stroma and migrate to the lining layer than in RA SM: However, the lymphocytic infiltrate in the SM of both groups is similar.
We report the first cytogenetic analysis of a leiomyosarcoma of the sinonasal tract, a rare neoplasm. Karyotypic analysis showed near-triploid and near-tetraploid modal chromosome numbers with extensive structural and numerical aberrations. Three consistent structural changes, including i(6p), der(10)ins(10;1)(q26;q23q44), and der(12)t(1;12)(q11;q24) were observed in most cells. A der(11)t(11;?)(p15;?) was observed in 14 of 20 cells. Clonal structural rearrangements, including i(1q), del(2)(q37), der(3)t(3;?)(p25;?), del(4)(q31), del(7)(q32), der(12)t(12;?)(p12;?), der(15), del(21)(q22), and der(X) were each observed in a few cells. Numerical changes, including trisomies for chromosomes 2-5, 7, 9, 11, 15, 17, 18, and 20 and monosomies 10 and 12 were observed. Comparison of our findings to those of leiomyosarcomas at different sites showed trisomies 7 and 20 and rearrangements of 11p12-p15 and 21q22.
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