Collision of desmoplastic-neurotropic melanoma and squamous cell carcinoma on the lip.

We report on a case of the collision of a desmoplastic-neurotropic melanoma and a squamous cell carcinoma on the lip. A 46-year-old male developed a multifocal infiltrative squamous cell carcinoma of the lower lip, which also showed sparse melanocyte atypia within the epidermis and an extensive spindle cell proliferation within the dermis, subcutaneous tissues and nerves. An immunohistochemical panel showed that the spindle cells were melanocytes, not derived from the squamous cell carcinoma.

Fibroblasts from non-healing human chronic wounds show decreased expression of beta ig-h3, a TGF-beta inducible protein.

Background: Increasing evidence shows persistent phenotypic alterations in fibroblasts from non-healing human chronic wounds, which may result in faulty extracellular matrix deposition and keratinocyte migration. We have previously shown that these cells are characterized by morphological changes, low proliferative potential and unresponsiveness to TGF-beta1, and down regulated phosphorylation of Smad 2/3 and p42/44 MAPK from decreased expression of the TGF-beta type II receptor.

Objective: To identify genes and proteins that may be differentially expressed in chronic wounds and their cultured fibroblasts.

Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds.

The nonhematopoietic component of bone marrow includes multipotent mesenchymal stem cells (MSC) capable of differentiating into fat, bone, muscle, cartilage, and endothelium. In this report, we describe the cell culture and characterization, delivery system, and successful use of topically applied autologous MSC to accelerate the healing of human and experimental murine wounds. A single bone marrow aspirate of 35-50 mL was obtained from patients with acute wounds (n = 5) from skin cancer surgery and from patients with chronic, long-standing, nonhealing lower extremity wounds (n = 8).

Migration of the epidermal over the dermal component (epiboly) in a bilayered bioengineered skin construct.

A bilayered bioengineered living skin construct (LSC) consisting of viable human neonatal keratinocytes over a collagenous dermis seeded with dermal fibroblasts has been used extensively in difficult-to heal human wounds. Its biological properties include production of several mediators, cytokines, and growth factors and the ability to heal itself upon injury. In this study, we investigated the process of keratinocyte migration in LSC.

Human beta-defensin-2 expression is increased in chronic wounds.

First identified in psoriatic epidermis and subsequently in other inflammatory cutaneous lesions, human beta-defensin-2 (hbetaD-2) is one of two endogenous antimicrobial peptides related to defensins in plants and animals. Our objective was to determine the expression of hbetaD-2 after injury and in chronic wounds. Biopsies of normal ipsilateral thigh skin and wound edges were taken from nine consecutive patients with venous leg ulcers (day 1) and from the same biopsy sites 2 days later (day 3).

Full-thickness wounding of the mouse tail as a model for delayed wound healing: accelerated wound closure in Smad3 knock-out mice.

Experimentally induced wounds in animal models are useful in gaining a better understanding of the cellular and molecular processes of wound healing, and in the initial evaluation of the safety and effectiveness of potential therapeutic agents. However, studying delayed healing has proved difficult in animals, whose wounds heal within a few days. In this report, we describe a novel method for establishing mouse wounds that require up to 3 weeks or more for complete closure, and we show the validity of this model in Smad3 null mice, which are known to display accelerated healing.

Histologic progression of B16 F10 metastatic melanoma in C57BL/6 mice over a six week time period: distant metastases before local growth.

B16F10 murine metastatic melanoma in the tails of C57BL/6 mice after subcutaneous injection is a well-established model. However, the histologic progression from injected cells to established local growth of melanoma has not been studied systematically. We therefore have investigated the histologic changes and growth of B16F10 melanoma at the injection site over a six-week time period.

Significance of N-methyl-D-aspartate (NMDA) receptor-mediated signaling in human keratinocytes.

Increasing data suggest that glutamate might act as a cell-signaling molecule in non-neuronal tissues such as the skin. Here we demonstrate the presence of functional N-methyl-D-aspartate (NMDA)-type glutamate receptors in human keratinocytes. NMDA receptor expression strongly reflects the degree of cell-to-cell contact.

Participation of bone marrow derived cells in cutaneous wound healing.

Bone marrow has long been known to be a source of stem cells capable of regeneration of the hematopoeitic system. Recent reports, however, have indicated that bone marrow might also contain early stem cells that can differentiate into other organ tissues such as skin. While these studies have illustrated that bone marrow stem cells could find their way to the skin, they have not addressed the dynamics of how bone marrow stem cells might participate in the homeostatis and regeneration of skin.

Wounding of bioengineered skin: cellular and molecular aspects after injury.

Skin substitutes are increasingly being used in the treatment of difficult to heal wounds but their mechanisms of action are largely unknown. In this study, using histology, immunostaining, flow cytometry, enzyme-linked immunosorbent assay, and reverse transcription polymerase chain reaction, we determined the response to injury of a human bilayered skin substitute. Meshing or scalpel fenestration of the construct was found to stimulate keratinocyte migration and to decrease proliferation.

Lymphoepithelioma-like carcinoma of the colon in a patient with hereditary nonpolyposis colorectal cancer.

Tumors with features similar to those of nasopharyngeal carcinoma, so-called lymphoepithelioma-like carcinomas, have been described in several organs but are extremely rare in the colon. We describe a patient with a family history consistent with hereditary nonpolyposis colorectal cancer who had 3 malignant lesions in the right colon, namely, a mucinous cancer, a lymphoepithelioma-like carcinoma, and a well-differentiated adenocarcinoma with prominent lymphoid stroma. To the best of our knowledge, lymphoepithelioma-like carcinoma has not been described previously in hereditary nonpolyposis colorectal cancer.

Improved detection of CD5 epitope in formalin-fixed paraffin-embedded sections of benign and neoplastic lymphoid tissues by using biotinylated tyramine enhancement after antigen retrieval.

To evaluate the effectiveness of the immunohistochemical staining of B- and T-cell lymphomas with Leu-1 (clone L17F12 CD5 antibody, Becton Dickinson, San Jose, Calif) in formalin-fixed paraffin-embedded sections, we stained 12 specimens reflecting cases of chronic lymphocytic leukemia/small lymphocytic lymphoma, 7 of mantle cell lymphoma, 13 of T-cell lymphomas, and 9 of various B-cell neoplasms that do not ordinarily express CD5, using a streptavidin-horseradish peroxidase method with biotinylated tyramine enhancement after antigen retrieval. We were able to detect CD5 reactivity of neoplastic cells in 9 (75%) of 12 cases of chronic lymphocytic leukemia, 6 (86%) of 7 cases of mantle cell lymphoma, and 13 (100%) of 13 of the T-cell lymphomas. B-cell neoplasms (9/9) not typically associated with CD5 expression showed no reactivity of tumor cells.

Paraganglioma-Like Adenomas of the Thyroid (PLAT): Incidental Lesions with Unusual Features in a Patient with Nodular Goiter.

We discovered two well-demarcated nodules incidentally in a thyroid removed because of a nodular goiter. Histologically, the nodules showed a pattern of paraganglioma or so-called paraganglioma-like adenoma of the thyroid (PLAT), with lobules of polygonal and oval cells in a vascular stroma, but the immunohistochemical markers typical of paraganglioma, including chromogranin, synaptophysin, Leu 7 and 5-100, and thyroglobulin, characteristic of PLAT, were negative in the tumor cells. C-cell markers calcitonin and somatostatin were also negative.

Analysis of IL-2, IL-4 and their receptors in clonally-related cell lines derived from a patient with a progressive cutaneous T-cell lymphoproliferative disorder.

Three clonally related T-cell lymphoma lines (PB-1, 2A, and 2B) were examined for expression of IL-2, IL-4, and their receptors. All three lines were derived from a single patient who had an atypical, progressive T-cell lymphoproliferative disorder involving primarily skin (Davis, T.H.

Cutaneous CD56+ large T-cell lymphoma associated with high serum concentration of IL-2.

We report the case of a patient with a clinically aggressive large cell lymphoma (LCL) which expressed several T-lymphocyte markers and, in addition, CD56 and, to a lesser degree, CD68 antigens. A marked increase in serum concentration of interleukin (IL)-2 was found (490 and 167 pg/0.1 mL in two serum samples collected 6 months apart).

The t(2;5) chromosomal translocation is not a common feature of primary cutaneous CD30+ lymphoproliferative disorders: comparison with anaplastic large-cell lymphoma of nodal origin.

Primary cutaneous CD30+ lymphoproliferative disorders (LPDs), including lymphomatoid papulosis (LyP), anaplastic and nonanaplastic CD30+ large-cell lymphoma, and borderline cases, comprise a clinical and histologic spectrum. Primary cutaneous and primary nodal CD30+ anaplastic large-cell lymphomas (ALCLs) are distinct clinical entities that have identical morphologic features but differ in age of onset, immunophenotype, and prognosis. It can be difficult to distinguish primary cutaneous from nodal ALCLs that secondarily involve the skin, which is important because these diseases differ significantly in response to treatment and clinical outcome.

Expression of Hodgkin's disease associated antigen BLA.36 in anaplastic large cell lymphomas and lymphomatoid papulosis primarily of T-cell origin.

Monoclonal antibody BLA.36 stains Reed-Sternberg (RS) cells and their mononuclear variants, as well as some benign and malignant cells of B-cell lineage, and retains its immunoreactivity in formalin- and B5-fixed tissue. The origin of the RS cell is controversial and the distinction between Hodgkin's disease (HD), anaplastic large cell lymphoma (ALCL), and lymphomatoid papulosis (LyP) (the latter two primarily T-cell in origin), can be difficult.

Constitutive secretion of soluble interleukin-2 receptor by human T cell lymphoma xenografted into SCID mice. Correlation of tumor volume with concentration of tumor-derived soluble interleukin-2 receptor in body fluids of the host mice.

Increased serum concentration of soluble alpha-chain receptor for interleukin-2 (sIL-2R) has been noted in patients with a variety of inflammatory conditions and lymphoid malignancies including T cell leukemia and lymphoma. Elevated sIL-2R serum levels seen in lymphoid malignancies appear to correlate with the clinical stage of disease. However, because sIL-2R is produced by normal activated lymphocytes, it has been uncertain whether serum sIL-2R in such conditions is derived from tumor cells or normal immune cells responding to the tumor.

Eosinophils are the major source of transforming growth factor-beta 1 in nodular sclerosing Hodgkin's disease.

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cytokine which promotes fibroblast growth and collagen synthesis, but suppresses growth and differentiation of immune lymphocytes and killer cells. Immunohistochemical detection of TGF-beta 1 in Hodgkin's disease (HD) has been shown to correlate with the histologic feature of nodular sclerosis, which is associated with a favorable prognosis (American Journal of Pathology 1990, 136:1209). In that study, TGF-beta 1 was localized mainly at the margins of broad collagen bands (presumably sites of new collagen synthesis) and in areas containing numerous Hodgkin/Reed-Sternberg cells (H/RS).

Leu-22: a preferential marker for T-lymphocytes in paraffin sections. Staining profile in T- and B-cell lymphomas, Hodgkin's disease, other lymphoproliferative disorders, myeloproliferative diseases, and various neoplastic processes.

Monoclonal antibody Leu-22 represents an effective reagent for detection of neoplastic and nonneoplastic T-cells in paraffin sections of routinely processed tissues (242 specimens evaluated). In nonneoplastic tissues, immunoreactivity was localized mainly to lymphoid cells corresponding to a T-cell distribution. Immunoreactivity in lymphoid neoplasms, however, was preferentially, but not exclusively, limited to T-cell populations.